Head And Neck Tumors Research Articles

Abstract B028: Expression of NOTCH1 in head and neck tumours at selected hospitals in Ghana

Abstract Head and neck tumors (HNT) are of paranasal sinuses origin (the salivary glands and the upper aerodigestive tract). It constitutes the sixth most common tumors. Studies have shown that, factors such as tobacco and alcohol intake and viral infections may increase the relative risk to the tumor. Notch1 pathways are frequently altered in many tumors, however, the clinical significance of NOTCH1dysregulation in head and neck tumors is poorly understood. METHOD: The aim of this study was to investigate the expression NOTCH1 in head and neck tumor and also to elucidate the various anatomical pattern of the head and neck tumors in selected hospitals in Ghana. NOTCH1 expression were analyzed using quantitative real-time PCR (qRT-PCR) and immunohistochemical staining on tissue samples from a consecutive series of head and neck tumor patients resections over a four-year period. RESULTS: The percentage of low expression of Notch1 were 71.4% in the malignant tissue (n=98) and 76.9% (n=52) in the benign tissue. The anatomical site with high of low expression of the NOTCH1 was found in oral cavity (37.1%) followed by respiratory (27.1%) followed by mandible (14.3%). CONCLUSION: There were low expression of NOTCH1 in head and neck tumour tissues suggesting that NOTCH1may be a tumor suppressor gene. We further propose that, NOTCH1 offers a potential tool as a target molecule in the development of therapies for head and neck tumors. Citation Format: Precious Barnes, Roland Osei Saahene. Expression of NOTCH1 in head and neck tumours at selected hospitals in Ghana [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Expanding and Translating Cancer Synthetic Vulnerabilities; 2024 Jun 10-13; Montreal, Quebec, Canada. Philadelphia (PA): AACR; Mol Cancer Ther 2024;23(6 Suppl):Abstract nr B028.

The Role of Estrogen and Estrogen Receptors in Head and Neck Tumors.

Head and neck squamous cell carcinoma (HNSCC) is the most common histological form of head and neck tumors (HNTs), which originate from the epithelium of the lips and oral cavity, pharynx, larynx, salivary glands, nasal cavity, and sinuses. The main risk factors include consumption of tobacco in all forms and alcohol, as well as infections with high-risk human papillomaviruses or the Epstein-Barr virus. Regardless of the etiological agent, the risk of developing different types of HNTs is from two to more than six times higher in males than in females. The reason for such disparities probably lies in a combination of both biological and psychosocial factors. Therefore, it is hypothesized that exposure to female sex hormones, primarily estrogen, provides women with protection against the formation and metastasis of HNTs. In this review, we synthesized available knowledge on the role of estrogen and estrogen receptors (ERs) in the development and progression of HNTs, with special emphasis on membrane ERs, which are much less studied. We can summarize that in addition to epidemiologic studies unequivocally pointing to the protective effect of estrogen in women, an increased expression of both nuclear ERs, ERα, and ERβ, and membrane ERs, ERα36, GPER1, and NaV1.2, was present in different types of HNSCC, for which anti-estrogens could be used as an effective therapeutic approach.

Abstract 6454: Genomic characterization of vulvar squamous cell carcinoma

Abstract Introduction: Understanding the molecular underpinnings of vulvar squamous cell carcinoma (vSCC) has strong potential for clinical impact, given the unmet need for this rare cancer. vSCCs have two main etiologies, including human papillomavirus (HPV) infection or skin conditions such as lichen sclerosis. Clinically, few treatment options with limited efficacy are available for recurrent vSCCs and large whole transcriptome disease subtyping studies are limited due to the rarity of this cancer type. Here, we present a whole transcriptome subtyping study of 244 vSCC clinical samples with DNA genomic profiling. Furthermore, we compared vSCCs to other SCC disease subtypes (pan-SCC), including lung, esophageal, skin, urothelial, anal, and head and neck (HN). Our goal was to gain novel insights into the molecular landscape of vSCCs to inform new routes of therapy. Methods: Deidentified records of SCC patients were selected from the Tempus clinico-genomic database. The vSCC cohort was predominantly composed of, but not exclusively, naive or pre-treatment primary tissue. The pan-SCC cohort was limited to randomly sampled primary pre-treatment female samples with paired RNA and DNA sequencing. To perform vSCC subtyping, we used bulk RNA-seq and clustered the samples using FastPG-CC, an internally developed consensus-clustering extension of FastPG, a graph-based parallelized clustering tool. We next performed differential expression, pathway analysis, and cell type abundance estimation. Results: Unbiased gene expression clustering analysis identified three vSCCs clusters; an HPV+ cluster (HPV+, 32% of vSCC samples), HPV- cluster (HPV-, 33%), and an intermediate cluster which contained both HPV+ and HPV- samples (Mix, 35%). The HPV- cluster was enriched for TP53 and TERT promoter mutations, EMT and tumor microenvironment gene expression-derived pathways, and was most similar to HPV- oral HN tumors. The HPV+ cluster was enriched with PIK3CA mutations, cell cycle gene expression and was most similar to other HPV+ SCC samples, including cervical, anal, and HN. The Mix cluster was enriched for neutrophils, fatty acid metabolism and was most similar to skin SCC. Conclusions: We performed a multi-modal molecular subtyping analysis on a large cohort of vSCCs and identified three molecular subtypes, which enabled us to identify heterogeneity within vSCC, and observe that a subset of vSCCs share features with SCC tumor types for which there are emerging therapy options. Thus, this approach identifies a subset vSCCs that may be responsive to existing SCC therapeutics. Citation Format: Sara R. Selitsky, Tasha Thong, Kimberley Roche, Justin Guinney, Praveen Sethupathy, Catherine Igartua. Genomic characterization of vulvar squamous cell carcinoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 6454.

Expression of RAS and RAB interactor 1 (RIN1) in head and neck tumors at selected hospital in Ghana.

Head and neck tumors (HNT) are tumors of the paranasal sinuses, the salivary glands and the upper aerodigestive tract. RIN1 is a Ras effector protein regulating epithelial cell properties and has been implicated in a number of cancers. The aim of this study was to investigate the expression of RIN1 in head and neck tumors. RIN1 expression was assessed using quantitative real-time PCR (qRT-PCR) and immunohistochemical staining on archival head and neck tissue samples between 2014 and 2020. RIN1 expression was low in tissue samples as compared with the normal head and neck tissues. High and low RIN1 levels were compared with ages ≤40, >40 in the head and neck tumors of p-value 0.02. There was a significant difference with p-values of 0.001 when poor and well-moderate malignant tumors were compared. Our data suggests that RIN1may play an important role in head and neck tumor progression and that its expression may provide baseline data to facilitate identification of new molecular targeted therapeutics.

Is noncoplanar plan more robust to inter-fractional variations than coplanar plan in treating bilateral HN tumors with pencil-beam scanning proton beams?

Noncoplanar plans (NCPs) are commonly used for proton treatment of bilateral head and neck (HN) malignancies. NCP requires additional verification setup imaging between beams to correct residual errors of robotic couch motion, which increases imaging dose and total treatment time. This study compared the quality and robustness of NCPs with those of coplanar plans (CPs). Under an IRB-approved study, CPs were created retrospectively for 10 bilateral HN patients previously treated with NCPs maintaining identical beam geometry of the original plan but excluding couch rotations. Plan robustness to the inter-fractional variation (IV) of both plans was evaluated through the Dose Volume Histograms (DVH) of weekly quality assurance CT (QACT) sets (39 total). In addition, delivery efficiency for both plans was compared using total treatment time (TTT) and beam-on time (BOT). No significant differences in plan quality were observed in terms of clinical target volume (CTV) coverage (D95) or organ-at-risk (OAR) doses (p>0.4 for all CTVs and OARs). No significant advantage of NCPs in the robustness to IV was found over CP, either. Changes in D95 of QA plans showed a linear correlation (slope=1.006, R2 >0.99) between NCP and CP for three CTV data points (CTV1, CTV2, and CTV3) in each QA plan (117 data points for 39 QA plans). NCPs showed significantly higher beam delivery time than CPs for TTT (539±50vs. 897±142s; p<0.001); however, no significant differences were observed for BOT. NCPs are not more robust to IV than CPs when treating bilateral HN tumors with pencil-beam scanning proton beams. CPs showed plan quality and robustness similar to NCPs while reduced treatment time (∼6min). This suggests that CPs may be a more efficient planning technique for bilateral HN cancer proton therapy.

Mitotic Errors Increase Radiation Sensitivity in Multiple Cancer Cell Types and in Laryngeal Cancer Patients

Chromosomal instability (CIN) arises from continual mitotic errors over the course of multiple cell divisions and is common in cancer. When CIN is increased beyond a maximally tolerated threshold it leads to cell death due to loss of both copies of one or more essential chromosomes. Combining two independent insults that each cause tolerable levels of CIN results in high CIN, cell death and tumor suppression. Because radiation causes CIN, we hypothesize that pre-existing CIN sensitizes tumor cells to radiation therapy. We characterized CIN in 4 HPV+ and 4 HPV- head and neck (HNC), 4 cervical, and 2 breast cancer cell lines before and 24 hours after 2 Gy of radiation. CIN was quantified by scoring lagging, bridge, and misaligned chromosomes, centrosome amplification, and multipolar spindles using immunofluorescence microscopy. To test our hypothesis, we created isogenic CIN and non-CIN HeLa and FaDu cells by knocking down the mitotic checkpoint protein Mad1, which induces lagging chromosomes, and by using MCF10A cells expressing tet-inducible polo-like kinase 4 (PLK4) to induce centrosome amplification. Clonogenic assays and murine tumor growth curves were used to determine radiation sensitivity in vitro and in vivo respectively. 6-chromosome FISH was used to quantify CIN and test if it was associated with local recurrence (LR) in a cohort of 29 laryngeal cancer patients treated with definitive (chemo)radiation. Significant differences were determined using a two-tailed student's t-test or Fisher's exact test. A total of 2 Gy of radiation significantly increased lagging, bridge, and misaligned chromosomes and induced centrosome amplification in all cancer cell types in vitro and in vivo. Most abnormal chromosomes after radiation were acentric fragments, which are known to missegregate. Mad1 knockdown in HeLa and FaDu cells increased CIN and led to significantly increased radiation sensitivity compared to their wild-type counterparts. PLK4 overexpression in MCF10A cells led to centrosome amplification and multipolar spindles, which also increased radiation sensitivity. Additionally, mitotic errors were significantly correlated with radiation response in both HPV+ and HPV- patient derived xenograft (PDX) HNC tumors. Finally, patients with laryngeal tumors with CIN below the median of the cohort had a 31% rate of LR after therapy, while tumors with CIN greater than or equal to the median had a LR rate of only 6%. Cancer cells with higher CIN are more sensitive to radiation therapy in vitro and in vivo. This was true for different types of mitotic errors and in different cancer models implying this is likely tumor type agnostic. Importantly, laryngeal tumors with higher baseline levels of CIN had an improved response to definitive radiation therapy, implying increased radiation sensitivity. These studies have potential implications for personalization of radiation dose.

Clinical Review on Head and Neck CBCT Images

Optimal quality assurance is vital in head and neck (HN) radiotherapy (RT), as inferior dosimetry has proven to compromise survival in HN cancer patients. Image guidance using cone-beam computed tomography (CBCT) has enabled precise matching of tumor targets. The objective was to analyze the translational and rotational shifts obtained from HN CBCT in order to develop the 6D HN imaging protocol, henceforth to achieve the best precision radiotherapy. Sixty patients who received treatment from January 2021 to September 2022 were randomly selected - 10 from each sub-site (paranasal sinuses, nasopharynx, oropharynx, oral cavity, larynx-hypopharynx-thyroid and early-stage glottis). Weekly CBCT obtained were analyzed using offline automatic image registration (IR) on an electronic patient information management system. First, 2 regions of interests (ROIs) were defined; one was based on departmental HN IGRT protocol and the other covered the entire planning target volume (PTV). Subsequently, IR was performed with 2 different algorithms; Maximum Mutual Information (MMI) (soft tissue-based) and Chamfer (bone-based). Each CBCT was inspected manually by an individual to avoid inter-observer variability. The shifts were reported as mean ± standard deviation (SD). Paired t-test was used to analyze the variances in translational and rotational displacements between the different ROIs and algorithm. Early-stage glottis was excluded in the ROI comparison as the treatment field was small and the ROI covered the entire PTV. Overall setup errors were 1.2 ± 1.1mm for the translational shifts and 0.7 ± 0.6° for the rotational. The overall frequency of displacement was 95.2% ≤2° and 99.5% ≤5mm. MMI was more constant than Chamfer for HN CBCT matching as reflected by a considerably smaller translational (1.09 ± 1.05mm vs 1.26 ± 1.16mm, p<0.001) and rotational (0.67 ± 0.57° vs 0.77 ± 0.70°, p<0.001) shifts. The comparison of defining ROIs (PTV vs Protocol) was insignificant in the translational shifts (p = 0.057). However, a substantial difference was observed in the rotational displacements (p = 0.003). The analysis was fundamental in identifying the optimal matching tool and it supports the HN 6D imaging protocol. This audit validated the current 5mm tolerance for translational shift and further established a 2° tolerance for the rotational shift for HN 6D CBCT matching. Profoundly, soft tissue localization is of the utmost importance for highly conformal modulated RT, and adaptation of soft tissue matching is strongly encouraged for HN tumors located in these regions.

Synthetic MRI plus FSE-PROPELLER DWI for differentiating malignant from benign head and neck tumors: a preliminary study.

Preoperative classification of head and neck (HN) tumors remains challenging, especially distinguishing early cancerogenic masses from benign lesions. Synthetic MRI offers a new way for quantitative analysis of tumors. The present study investigated the application of synthetic MRI and stimulus and fast spin echo diffusion-weighted imaging with periodically rotated overlapping parallel lines with enhanced reconstruction (FSE-PROPELLER DWI) to differentiate malignant from benign HN tumors. Forty-eight patients with pathologically confirmed HN tumors were retrospectively recruited between August 2022 and October 2022. The patients were divided into malignant (n = 28) and benign (n = 20) groups. All patients were scanned using synthetic MRI and FSE-PROPELLER DWI. T1, T2, and proton density (PD) values were acquired on the synthetic MRI and ADC values on the FSE-PROPELLER DWI. Benign tumors (ADC: 2.03 ± 0.31 × 10-3 mm2/s, T1: 1741.13 ± 662.64 ms, T2: 157.43 ± 72.23 ms) showed higher ADC, T1, and T2 values compared to malignant tumors (ADC: 1.46 ± 0.37 × 10-3 mm2/s, T1: 1390.06 ± 241.09 ms, T2: 97.64 ± 14.91 ms) (all P<0.05), while no differences were seen for PD values. ROC analysis showed that T2+ADC (cut-off value, > 0.55; AUC, 0.950) had optimal diagnostic performance vs. T1 (cut-off value, ≤ 1675.84 ms; AUC, 0.698), T2 (cut-off value, ≤ 113.24 ms; AUC, 0.855) and PD (cut off value, > 80.67 pu; AUC, 0.568) alone in differentiating malignant from benign lesions (all P<0.05); yet, the difference in AUC between ADC and T2+ADC or T2 did not reach statistical significance. Synthetic MRI and FSE-PROPELLER DWI can quantitatively differentiate malignant from benign HN tumors. T2 value is comparable to ADC value, and T2+ADC values could improve diagnostic efficacy., apparent diffusion coeffificient, head and neck tumors.

The impact of the temporal sequence of cranial radiotherapy and platin-based chemotherapy on hearing impairment in pediatric and adolescent CNS and head-and-neck cancer patients: A report from the PanCareLIFE consortium.

The impact of the temporal sequence by which cranial radiotherapy (CRT) and platin-based chemotherapy (PCth) are administered on sensorineural hearing loss (SNHL) in pediatric and adolescent central nervous system (CNS) and head-and-neck (HN) cancer patients has not yet been studied in detail. We examined the ototoxic effects of sequentially applied CRT and PCth. This study included children and adolescents with CNS and HN tumors who participated in the multicountry PanCareLIFE (PCL) consortium. Audiological outcomes were compared between patients who received CRT prior to PCth and those who received it afterwards. The incidence, degree and posttreatment progression of SNHL, defined as Muenster classification grade ≥MS2b, were evaluated in 141 patients. One hundred and nineteen patients were included in a time-to-onset analysis. Eighty-eight patients received CRT prior to PCth (Group 1) and 53 patients received PCth before CRT (Group 2). Over a median follow-up time of 1.6 years, 72.7% of patients in Group 1 experienced SNHL ≥ MS2b compared to 33.9% in Group 2 (P < .01). A time-to-onset analysis was performed for 74 patients from Group 1 and 45 patients from Group 2. Median time to hearing loss (HL) ≥ MS2b was 1.2 years in Group 1 and 4.4 years in Group 2 (P < .01). Thus, audiological outcomes were better for patients who received CRT after PCth than before. This finding should be further evaluated and considered within clinical practice in order to minimize hearing loss in children and adolescents with CNS and HN tumors.

Primary tumor site for localized Merkel cell carcinoma drives different management strategies without impacting oncologic outcomes

Background and purposeClinically localized Merkel cell carcinoma (MCC) has been associated with high rates of disease relapse. This study examines how primary tumor anatomic site drives patterns of care and outcomes in a large cohort treated in the contemporary era. Materials and methodsPatterns of care and associated outcomes were evaluated for clinically Stage I-II MCC patients treated at our institution with adjuvant radiation therapy (RT) to the primary site and/or regional nodal basin as a component of their curative intent therapy between 2014–2021. ResultsOf 80 patients who met inclusion criteria, the primary tumor anatomic site was head and neck (HN) for 42 (53%) and non-head and neck (NHN) for 38 (47%). Primary tumor risk factors were similar between cohorts. Fewer patients with HN tumors had wide local excision (WLE; HN-81% vs. NHN-100% p < 0.01). Of those undergoing WLE, patients with HN tumors received higher dose adjuvant RT (>50 Gy: HN-70% vs. NHN-8%; p < 0.01). Patients with HN tumors were less likely to undergo sentinel lymph node biopsy (HN-62%vs. NHN-100%; p < 0.01) and more likely to have elective nodal RT (HN-48% vs. NHN-0%). Despite varying management strategies, there was no significant difference in local recurrence-free survival (3-yr LRFS HN-94% vs. NHN-94%; p = 0.97), nodal recurrence-free survival (3-yr NRFS HN-89% vs. NHN-85%; p = 0.71) or overall recurrence-free survival (3-yr RFS 73% HN vs. 80% NHN; p = 0.44). ConclusionsAmong patients with primary MCC who had RT as a component of their initial treatment strategy, anatomically-driven heterogeneous treatment approaches were associated with equally excellent locoregional disease control.

The patterns of head and neck tumours in Northern Ghana: a histopathological review in a tertiary referral hospital in Northern Ghana

&lt;p class="abstract"&gt;&lt;strong&gt;Background:&lt;/strong&gt; There is paucity of published data on head and neck tumours (HNTs) in Ghana, even the few studies available were conducted in the middle and southern belts of the country. The present study in northern Ghana, was conducted to study the histopathological characteristics of HNTs and offer recommendations.&lt;/p&gt;&lt;p class="abstract"&gt;&lt;strong&gt;Methods:&lt;/strong&gt; This retrospective study analysed HNTs for the past 10 years at the Tamale Teaching Hospital in northern Ghana. &lt;/p&gt;&lt;p class="abstract"&gt;&lt;strong&gt;Results:&lt;/strong&gt; There were 576 HNTs, with 66.0% benign and 34.0% malignant. The mean age (years) was 34.9±21.6. Females were commonly affected 53.6%. Benign tumours were diagnosed in relatively young patients with mean age of 29.6±19.2, compared to 44.9±22.6 for the malignant tumours. Patients commonly present late with HNTs. The common anatomical sites were: odontogenic and maxillofacial bone (18.4%), oral cavity and mobile tongue (18.1%), and hypopharynx and larynx (13.9%). The histopathological subtypes were: squamous papilloma (13.9%), squamous cell carcinoma (SCC) (12.8%), and salivary gland pleomorphic adenoma (9.4%). The common benign tumours were; squamous papilloma (21.1%), salivary glands pleomorphic adenoma (14.2%), and benign vascular tumours (13.9%). For malignant tumours the order was; SCC (37.8%), lymphoma (11.2%) and olfactory neuroblastoma (10.2%). A significant number of patients had no history of cigarette smoking (p&amp;lt;0.0001).&lt;/p&gt;&lt;p class="abstract"&gt;&lt;strong&gt;Conclusions:&lt;/strong&gt; Benign tumours were the common neoplastic lesions within the head and neck region. HNTs were common in relatively young patients and in females. Benign tumours were diagnosed in relatively young patients compared to malignant tumours. Patient with malignant tumours presented early to health facilities, compared to those with benign tumours.&lt;/p&gt;

ASSESSING RISK FACTOR FOR DYSGEUSIA IN SYSTEMIC TREATMENT OF HEAD AND NECK CANCER: A CROSS-SECTIONAL STUDY

Objectives To evaluate risk factors associated with dysgeusia in patients with head and neck tumors (HNTs) treated with chemotherapy. Study Design We performed a cross-sectional, retrospective, and quantitative study evaluating the incidence of dysgeusia by toxicity scale of the Common Terminology Criteria for Adverse Events: (0) no change in taste, (1) change in taste without change in diet and (2) change in taste and change in diet. Clinical-sociodemographic and therapeutic approaches were evaluated by chi-square test and multinomial logistic regression (P < .05; SPSS 20.0). Results Of 486 patients, 140 presented dysgeusia (28.8%), 91 of which were grade 1 and 49 were grade 2. The most frequent chemotherapeutic agents in HNT were cisplatin (63.8%) and carboplatin (27.8%), and radiotherapy was performed in 94.7%. Radiotherapy (P = .017) and cisplatin (P = .001) were the risk factors for dysgeusia grades 1 and 2. In the multivariate analysis, cisplatin increased the risk of dysgeusia in grade 23.20 times (95% CI, 1.45-7.04). Conclusions Cisplatin is the greatest risk factor for dysgeusia in systemic treatment for HNT, which is important knowledge because the loss of taste increases the risk of cachexia. To evaluate risk factors associated with dysgeusia in patients with head and neck tumors (HNTs) treated with chemotherapy. We performed a cross-sectional, retrospective, and quantitative study evaluating the incidence of dysgeusia by toxicity scale of the Common Terminology Criteria for Adverse Events: (0) no change in taste, (1) change in taste without change in diet and (2) change in taste and change in diet. Clinical-sociodemographic and therapeutic approaches were evaluated by chi-square test and multinomial logistic regression (P < .05; SPSS 20.0). Of 486 patients, 140 presented dysgeusia (28.8%), 91 of which were grade 1 and 49 were grade 2. The most frequent chemotherapeutic agents in HNT were cisplatin (63.8%) and carboplatin (27.8%), and radiotherapy was performed in 94.7%. Radiotherapy (P = .017) and cisplatin (P = .001) were the risk factors for dysgeusia grades 1 and 2. In the multivariate analysis, cisplatin increased the risk of dysgeusia in grade 23.20 times (95% CI, 1.45-7.04). Cisplatin is the greatest risk factor for dysgeusia in systemic treatment for HNT, which is important knowledge because the loss of taste increases the risk of cachexia.

Mesenchymal chondrosarcoma of the head and neck with HEY1::NCOA2 fusion: A clinicopathologic and molecular study of 13 cases with emphasis on diagnostic pitfalls.

Mesenchymal chondrosarcoma (MCS) is a rare translocation-associated sarcoma, driven by a canonical HEY1::NCOA2 fusion. The tumors typically have a biphasic phenotype of primitive small blue round cells intermixed with hyaline cartilage. The head and neck (HN) region is a common site for MCS, accounting for 12-45% of all cases reported. We assembled a relatively large cohort of 13 molecularly confirmed HN MCS for a detailed clinicopathologic analysis. The underlying fusion events were determined using fluorescence in situ hybridization and/or targeted RNA sequencing. The median age of presentation was 19 years. Five MCSs (39%) had an intraosseous presentation (skull, maxilla, palate, and mandible), while the remaining eight cases occurred in the brain/meninges, orbit, and nasal cavity. Microscopically, HN MCSs were characterized by primitive round cells arranged in a distinctive nested architecture and a rich staghorn vasculature. A cartilaginous component of hyaline cartilage islands and/or single chondrocytes were present in 69% cases. A combined immunoprofile of CD99(+)/SATB2(+)/CD34(-)/STAT6(-) was typically noted. As this immunoprofile is non-specific, the referral diagnoses in cases lacking a cartilaginous component included Ewing sarcoma family and osteosarcoma. Among the seven patients with follow-up data, three developed distant metastasis and one died of disease. HN MCS may arise at intra- or extra-osseous sites. The HN MCS appears to have a more prolonged survival compared other MCS sites. Testing for HEY1::NCOA2 fusion is recommended in HN tumors with nested round cell morphology and staghorn vasculature that lack a distinctive cartilaginous component.

Nicotinamide N-Methyltransferase in Head and Neck Tumors: A Comprehensive Review.

The head and neck tumors (HNT) are a heterogeneous group of diseases ranging from benign to malignant lesions, with distinctive molecular and clinical behaviors. Several studies have highlighted the presence of an altered metabolic phenotype in HNT, such as the upregulation of nicotinamide N-methyltransferase (NNMT). However, its biological effects have not been completely disclosed and the role of NNMT in cancer cell metabolism remains unclear. Therefore, this comprehensive review aims to evaluate the available literature regarding the biological, diagnostic, and prognostic role of NNMT in HNT. NNMT was shown to be significantly overexpressed in all of the evaluated HNT types. Moreover, its upregulation has been correlated with cancer cell migration and adverse clinical outcomes, such as high-pathological stage, lymph node metastasis, and locoregional recurrences. However, in oral squamous cell carcinoma (OSCC) these associations are still debated, and several studies have failed to demonstrate the prognostic significance of NNMT. The shRNA-mediated gene silencing efficiently suppressed the NNMT gene expression and exhibited a clear inhibitory effect on cell proliferation, promoting the expression of apoptosis-related proteins and modulating the cell cycle. NNMT could represent a new molecular biomarker and a new target of molecular-based therapy, although further studies on larger patient cohorts are needed to explore its biological role in HNT.

Single Fraction Radiotherapy as Postoperative Treatment (SF-PORT) for Resected, Stage I/II Merkel Cell Carcinoma

In the absence of randomized prospective data, the role of postoperative radiotherapy (PORT) for localized Merkel cell carcinoma (MCC) is controversial with varying practice patterns. Although a majority of patients with resected stage I/II MCC without adverse features may be cured with surgery alone, those with adverse features including head and neck (HN) primary tumors have local recurrence rates of 20% or more without PORT (Takagishi et al. Adv Radiat Oncol, 2016). Extrapolating from our experience demonstrating high rates of local control with single fraction radiotherapy (SFRT) for metastatic MCC (Iyer et al. Cancer Med, 2015), we hypothesized that SFRT (8 Gy) may be effective as PORT to optimize local control for stage I/II MCC with adverse risk features (e.g., HN disease, immunosuppression, recurrent disease, non-oncologic resection, lymphovascular space invasion (LVSI)), especially in patients for whom a conventional RT course may not be feasible.A single-institution, retrospective review of patients with clinical or pathological stage I/II MCC receiving SFRT (8 Gy) as postoperative treatment (SF-PORT) was completed from a prospectively-enrolled database.Thirty patients (median age 78 years) were identified who received SFRT after wide local excision (n = 24; 80%), Mohs surgery (n = 1; 3%), shave or excisional biopsy only (n = 5; 17%) of the primary. Patients had pathological stage I (n = 15; 50%), clinical stage I (n = 10: 33%), pathological stage II (n = 3; 10%) or clinical stage II (n = 2; 7%) disease. All patients received SF-PORT (8 Gy) at a median of 43 days (range: 14-203) following resection or biopsy. Five patients (4 with HN disease) received SFRT to draining lymph nodes. The majority of patients had HN tumors (77%), LVSI was present in 23%,17% were immunosuppressed and 7% had locally recurrent disease (n = 2). At median follow-up of 11.3 months (range: 3-45.7), no local or in-field recurrences were observed. No local or distant recurrences, MCC specific deaths, or RT related toxicities grade > 1 (CTCAE v5.0) were observed. There were two out-of-field regional nodal recurrences in HN patients who did not receive elective nodal RT.Our early experience demonstrates a high rate of in-field local control in patients with stage I/II MCC with adverse features managed with SF-PORT. This approach warrants further study.

Multiple Primary Malignancies in Head and Neck Cancer: A University Hospital Experience Over a Five-Year Period.

IntroductionWith an estimated incidence of 2%-4% per year, the development of a second primary malignancy (SPM) in patients with head and neck tumors (HNTs) is not a rare event. The present study aimed to (i) assess the frequency of SPMs in patients with HNTs treated in a university hospital over a five-year period and (ii) provide a demographic characterization of these patients.MethodsRetrospective single-centre study of patients with more than one primary tumor (including at least one HNT) diagnosed between January 1, 2015, and December 31, 2019. Data were retrieved from patients’ clinical records and anonymized for analysis purposes.ResultsA total of 53 out of 824 (6.43%) patients with multiple primary malignancies were identified, 18 of which synchronous and 35 metachronous. The median follow-up was 25 months. Thirteen patients were diagnosed with more than one HNT. Forty patients were diagnosed with at least one HNT and one non-HNT. The most frequently diagnosed non-HNT SPMs were lung cancer (n=17) and esophageal cancer (n=8). The five-year survival rate was 53% for patients with multiple HNSCCs and 47% for patients with at least one non-HNT (log-rank p=0.729). The median overall survival was 14 months for synchronous and 58 months for metachronous SPMs (log-rank p=0.002).ConclusionFindings from this study highlight the importance of long-term follow-up of HNT patients for early detection of SPMs, increasing the chance of providing treatment with curative intent and improving patient outcomes and survival.

Prognostic Worth of Epidermal Growth Factor Receptor (EGFR) in Patients with Head and Neck Tumors.

Introduction Head and neck tumors (HNT) are tumors that normally occur at the head and neck region of the body. Epidermal growth factor receptor (EGFR) has been found to be highly expressed in breast and other tumors; therefore, there is the need to investigate the level of EGFR expression among patients with head and neck tumors in Ghana. Method The level of EGFR expression was determined in head and neck tumor and control head and neck tissues with quantitative real-time PCR and immunohistochemistry analysis. Results The level of EGFR expressions was high in tumor tissues than in the control tissues. There was a significant difference of p value 0.025 among the ages >40 and ≤ 40 when the high and low level of EGFR was compared in the head and neck malignant tumor. The area under the curve for the high expression of EGFR among the malignant head and neck tumors was 0.901 with a specificity of 86.4%. Conclusion EGFR can serve as a prognostic marker in monitoring patients with HNT as well as a molecular therapeutic target.

Precision Radiotherapy: 18F-FDG PET-based radiotherapy planning in Head and Neck cancers.

Precision medicine is gaining importance in this era of molecular imaging where the molecular features of a disease can be noninvasively assessed and treated with personalized medicine. This is especially suited for head and neck cancers (HNCa). Early stage HNCa are ideally managed with radiotherapy (RT) or surgery. Head and neck (HN) is a complex region and its tumors respond to RT differently due to dissimilar structures and moving organs such as tongue. Radiation oncologists are always in the process of trying and investigating newer RT techniques in order to achieve precise and targetted therapy to tumour/s. One such innovation is Intensity modulated RT (IMRT) using 3 Dimensional conformal RT (3DCRT). This 3DCRT resizes the radiation beams to match the shape of the tumor. Such focused dose escalation may improve local control in HNCa. Image guided RT in conjunction with IMRT is the most advanced form of RT planning being used these days. Simulation computerized tomography (CT) images are usually incorporated into RT planning module. But limitations of CT such as poor soft tissue contrast than magnetic resonance imaging and inability to clearly define solid / cystic / necrotic areas and viable tumour exist. Functional imaging such as Positron Emission Tomography (PET) has established its superiority over CT in delineating the actual site and extent of HN tumors. A combination of IMRT with BTV (Biological Tumour Volume) may be the most ideal technique to deliver a homogeneous radiation boost to tumour. This review shall discuss PET based RT planning, challenges, practical tips, and how to optimize therapy with the least side effects to the normal surrounding tissues.

Repeat Radiation for Local Recurrence of Head and Neck Tumors and in Prostate Cancer.

Recent advances in diagnostic methods and in radiotherapy now increasingly enable repeat radiotherapy with curative intent for the treatment of previously irradiated lesions. In this review, we present data on oncological outcomes and on acute and late sequelae, as far as these are currently known, in patients with head and neck tumors (HNT) or prostate cancer (PCa) who underwent repeat radiotherapy after prior radiotherapy with curative intent. This review is based on clinical series with over 20 patients that were published between May 1998 and April 2018 (HNT) or between October 1998 and October 2018 (PCa) and were retrieved by a search in the PubMed database. Most of the clinical series retrieved were retrospective and uncontrolled. There were 16 studies that included 2678 patients with recurrent head and neck tumors, and 8 that included 245 patients with recurrent prostate cancer. In patients with squamous cell carcinoma of the head and neck, intensity-modulated radio - therapy (IMRT) and stereotactic body radiotherapy (SBRT) yielded three-year survival rates of 47-57% but also produced substantial acute and late adverse effects. Most of the studies concerning recurrent PCa involved small patient groups. In these studies, repeat radiotherapy with SBRT yielded tumor control rates of 40-80% after 11-24 months of follow-up, with only mild acute toxicity. Although no comparative studies are available, it seems that modern external beam radiotherapy techniques can be used for repeat radiotherapy of locally recurrent head and neck tumors with curative intent after careful patient selection. Repeat radiotherapy of PCa must still be considered experimental, but initial results from small-scale trials are encouraging. The long-term adverse effects cannot yet be accessed. Patients should be selected by an interdisciplinary tumor board. This type of treatment is generally carried out in a specialized center.

Viral co-infection with head and neck tumors

The review is devoted to assessing the prevalence of human papillomavirus (HPV) in combination with other viral agents for head and neck tumors (HNT). HPV is recognized as an etiological factor in the development of cervical cancer, but there is evidence that it may be involved in carcinogenesis in other locations, in particular the upper respiratory tract. However, HPV is not the most important factor in tumor growth and progression. Recently, many researchers have reported the presence of concomitant co-infection, affecting tumor progression. Of all the studies analyzed, only 3 studies showed the absence or low rates of co-infection in HNT: from the Czech Republic (0%), China (0.6%) and Japan (3%). Most often, HPV infection was detected together with the Epstein-Barr virus (EBV) - from 12.5 to 34.1% of cases. In Russia, the prevailing combination of viral co-infection was a combination of EBV and cytomegalovirus (9.5%) and a combination of EBV and herpes simplex virus (6.7%). Thus, the degree of incidence of HPV in HNT varies greatly, and the mechanisms of coinfection are poorly understood, which raises the question of whether HPV and concomitant infection can be involved in tumor progression. This makes further research in this direction relevant and promising.