Anatomic Subsite Research Articles

The risk and distribution of second primary cancers according to subsite of primary stomach cancer: a retrospective cohort population-based study

Background: The development of second primary cancers (SPCs) following a diagnosis of stomach cancer presents a significant clinical challenge, with varying risks depending on the anatomic subsite of the primary tumor, patient demographics, and treatment modalities. This study aims to assess the risk of SPCs in stomach cancer survivors, focusing on differences across anatomic subsites, gender, age, and treatment periods. Methods: We conducted a retrospective cohort study using data from stomach cancer patients, analyzing the incidence of SPCs based on the anatomic location of the primary tumor, with stratifications by gender, age, latency period, and year of diagnosis. Standardized incidence ratios (SIRs) were calculated to compare the observed SPC rates with those expected in the general population. Results: Elevated stomach SPC risk was observed across most anatomic subsites, particularly in the body (SIR 8.84) and fundus (SIR 7.34). Females exhibited higher SIRs compared to males, especially in the fundus (SIR 13.33 for females vs. 4.55 for males). Younger patients (<50 years) had significantly higher SPC risks, particularly for cancers originating in the fundus (SIR 49.56). Notably, patients diagnosed after 2010 showed the highest SIRs, indicating a potential impact of advances in diagnostic and therapeutic modalities. Non-stomach SPCs, including colorectal, lung, and thyroid cancers, were significantly elevated, with distinct patterns based on the primary tumor site. Conclusions: The study highlights the critical role of primary tumor location, gender, age, and treatment era in determining SPC risk in stomach cancer survivors. These findings underscore the need for tailored surveillance strategies to manage long-term cancer risks in this population.

Plasma ghrelin and risks of sex-specific, site-specific, and early-onset colorectal cancer: A Mendelian randomization analysis.

Epidemiological and laboratory-based studies have provided conflicting evidence for a role of ghrelin in colorectal cancer (CRC) development. We conducted two-sample Mendelian randomization (MR) analyses to evaluate evidence for an association of circulating ghrelin and CRC risk overall and by sex, cancer subsite and age at diagnosis. Genetic instruments proxying plasma total ghrelin levels were obtained from a recent genome-wide association study of 54,219 participants. Summary data for CRC risk were obtained from a recent meta-analysis of several genetic consortia (up to 73,673 cases and 86,854 controls). A two-sample MR approach and several sensitivity analyses were applied. We found no evidence for an association of genetically-predicted plasma total ghrelin levels and CRC risk (0.95, 95% confidence interval: 0.81-1.12; R2 of ghrelin genetic instruments: 4.6%), with similarly null results observed when stratified by sex, anatomical subsite, and for early-onset CRC. Our study suggests that plasma ghrelin levels are unlikely to have a causal relationship with overall, early-onset, and sex- and cancer subsite-stratified CRC risk. This large-scale analysis adds to the growing body of evidence that plasma total ghrelin levels are not associated with CRC risk.

Disparities in patient-reported distress in head and neck cancer.

257 Background: Distress is common among cancer patients, and impacts morbidity and mortality. Head and neck cancer (HNC) is considered one of the most emotionally distressing of all cancers, and given the stark racial disparities in HNC outcomes, we sought to examine racial and sociodemographic factors associated with clinically meaningful distress in a cohort of patients with HNC. Methods: We built a retrospective cohort of patients at a semi-urban, academic, National Cancer Institute (NCI)-designated comprehensive cancer center in the Southeastern United States. Cohort included patients with a diagnosis of HNC who received care from the Radiation Oncology department 5 weeks or less of initial diagnosis, from 2017 to 2022. Outcome of interest was clinically meaningful distress, a binary variable defined as a score of ≥4 on the distress thermometer (DT), a validated tool measuring distress, with scores ranging from 0-10. Main independent variables were sociodemographic factors (race/ethnicity, age, sex, marital status, and health insurance status). We further adjusted for clinical variables (stage of presentation, anatomical subsites, smoking and alcohol history), and problem list domain items. Using chi-square tests and multinomial regression analysis, we estimated differences in distress and odds of meaningful distress by sociodemographic factors, adjusting for clinical factors and problem list domains. Results: From a primary sample of 1,167 patients, 507 patients met our inclusion criteria. Nearly half (45.8%) of our sample had clinically meaningful distress, with a median DT score of 3 (IQR, 0-6). Total number of problem list items and physical concerns showed significant racial differences ( p < 0.05); however, in our final models, race was not significantly associated with clinically meaningful distress. Compared to those unmarried, married patients were significantly less likely to report distress (aOR = 0.62; 95% CI: 0.40, 0.95). Also, patients with emotional problems had double the odds of reporting clinically meaningful distress (aOR = 2.03; 95% CI: 1.02, 4.08). Other factors associated with significant clinical distress included tobacco history, and reported practical problems. Conclusions: Marital status and reported emotional problems are significantly associated with clinically meaningful distress in patients with HNC. Our study underscores the need for social support in mitigating distress and optimizing mental healthcare in our patient population. Further studies will explore distress trajectories across the HNC continuum and impact on HNC outcomes.

Reporting nasal pressure injuries in neonates receiving non-invasive ventilation: a scoping review.

Although neonates receiving Non-Invasive Ventilation (NIV) for respiratory support are at risk for nasal pressure injuries, efforts to standardize reporting are limited. A scoping review was conducted to identify the reporting systems used for describing these injuries. PubMed, Embase, and Web of Science were queried for papers reporting nasal injury with NIV usage in neonates. The primary outcome was reporting system usage. 705 titles and abstracts were screened. 40 papers met inclusion criteria. Most studies were Randomized Clinical Trials (37.5%) or cohort studies (37.5%). Most commonly, nasal injuries were reported using a unique, descriptive scale developed by the authors (10 studies, 25%). The Fischer et al 2010 scale, a three-stage reporting system, was used in 8 studies (20%). While 15 studies (38.0%) reported on specific anatomic subsite injury, only 2 studies (5.0%) employed endoscopy for assessment. Wide heterogeneity in pressure injury reporting secondary to NIV exists across specialties, institutions, and literature.

Multi-regional genomic and transcriptomic characterization of a melanoma-associated oral cavity cancer provide evidence for CASP8 alteration-mediated field cancerization

BackgroundPrecancerous and malignant tumours arise within the oral cavity from a predisposed “field” of epithelial cells upon exposure to carcinogenic stimulus. This phenomenon is known as “Field Cancerization”. The molecular genomic and transcriptomic alterations that lead to field cancerization and tumour progression is unknown in Indian Oral squamous cell carcinoma (OSCC) patients.MethodsWe have performed whole exome sequencing, copy-number variation array and whole transcriptome sequencing from five tumours and dysplastic lesions (sampled from distinct anatomical subsites - one each from buccal anterior and posterior alveolus, dorsum of tongue–mucosal melanoma, lip and left buccal mucosa) and blood from a rare OSCC patient with field cancerization.ResultsA missense CASP8 gene mutation (p.S375F) was observed to be the initiating event in oral tumour field development. APOBEC mutation signatures, arm-level copy number alterations, depletion of CD8 + T cells and activated NK cells and enrichment of pro-inflammatory mast cells were features of early-originating tumours. Pharmacological inhibition of CASP8 protein in a CASP8-wild type OSCC cell line showed enhanced levels of cellular migration and viability.ConclusionCASP8 alterations are the earliest driving events in oral field carcinogenesis, whereas additional somatic mutational, copy number and transcriptomic alterations ultimately lead to OSCC tumour formation and progression.

A Multimodal Protocol Combining 99mTc-Tilmanocept with Indocyanine Green Fluorescence Lympho-Angiography for Sentinel Lymph Node Biopsy in Early-Stage Oral Cancer: A Case Series.

Sentinel lymph node biopsy (SLNB) is currently considered as a viable alternative to elective neck dissection (END) for the management of cN0 oral cavity squamous cell carcinoma (OCSCC). However, some difficulties were detected in sentinel lymph node (SLN) identification in floor of mouth (FOM) and ventral tongue tumors because of the so-called "shine-through radioactivity" of the injection site, which may mask nodal hotspots in proximity. We assessed the feasibility and the potential strengths of combining 99mTc-Tilmanocept with indocyanine green (ICG) fluorescence lympho-angiography in a dedicated multimodal protocol for SLNB in T1/T2N0 oral cancer to evaluate the synergistic role of each of these two tracers in providing the appropriate sensitivity and ease of learning, even in such a critical anatomical subsite. A detailed, stepwise description of our multimodal protocol is provided, together with the presentation of its application in two cases of early-stage ventral tongue tumors. Radioactive guidance with 99mTc-Tilmanocept was used preoperatively to perform planar lymphoscintigraphy and single-photon emission computed tomography/computed tomography and to define the nodal hotspot(s) and the surgical "roadmap". In addition, it was used intraoperatively to pinpoint the SLN location within each nodal hotspot with high specificity but limited spatial resolution. Optical guidance with ICG injection at the tumor bed and near-infrared fluorescence imaging was then added, providing intuitive intraoperative guidance within each nodal hotspot with high spatial resolution. Our small experience with this protocol is illustrated and future perspectives are highlighted.

Molecular characterization of the salivary adenoid cystic carcinoma immune landscape by anatomic subsites

Adenoid cystic carcinoma (AdCC) is a slow-growing salivary gland malignancy that relapses frequently. AdCCs of the submandibular gland exhibit unique differences in prognosis and treatment response to adjuvant radiotherapy compared to other sites, yet the role of tumor anatomic subsite on gene expression and tumor immune microenvironment (TIME) composition remains unclear. We used 87 samples, including 48 samples (27 AdCC and 21 normal salivary gland tissue samples) from 4 publicly available AdCC RNA sequencing datasets, a validation set of 33 minor gland AdCCs, and 39 samples from an in-house cohort (30 AdCC and 9 normal salivary gland samples). RNA sequencing data were used for single sample gene set enrichment analysis and TIME deconvolution. Quantitative PCR and multiplex immunofluorescence were performed on the in-house cohort. Wilcoxon rank-sum, nonparametric equality-of-medians tests and linear regression models were used to evaluate tumor subsite differences. AdCCs of different anatomic subsites including parotid, submandibular, sublingual, and minor salivary glands differed with respect to expression of several key tumorigenic pathways. Among the three major salivary glands, the reactive oxygen species (ROS)/nuclear factor erythroid 2-related factor 2 (NRF2) pathway signature was significantly underexpressed in AdCC of submandibular compared to parotid and sublingual glands while this association was not observed among normal glands. Additionally, the NRF2 pathway, whose expression was associated with favorable overall survival, was overexpressed in AdCCs of parotid gland compared to minor and submandibular glands. The TIME deconvolution identified differences in CD4+ T cell populations between AdCC of major and minor glands and natural killer (NK) cells among AdCC of minor, submandibular, and parotid glands while plasma cells were enriched in normal submandibular glands compared to other normal gland controls. Our data reveal key molecular differences in AdCC of different anatomic subsites. The ROS and NRF2 pathways are underexpressed in submandibular and minor AdCCs compared to parotid gland AdCCs, and NRF2 pathway expression is associated with favorable overall survival. The CD4+ T, NK, and plasma cell populations also vary by tumor subsites, suggesting that the observed submandibular AdCC tumor-intrinsic pathway differences may be responsible for influencing the TIME composition and survival differences.

Association of soy intake and cooking methods with colorectal polyp and adenoma prevalence: findings from the extended Lanxi pre-colorectal cancer cohort (LP3C).

Limited research has explored the association between dietary soy products and colorectal polyps and adenomas, with insufficient attention given to cooking methods and subtypes of polyps. This study aimed to comprehensively assess the relationship between soy intake, its cooking methods, and the risk of colorectal polyps and adenomas within a high-incidence population of colorectal cancer (CRC) in China. Data were derived from 14,903 participants aged 40-80 years, enrolled in the extended Lanxi Pre-colorectal Cancer Cohort (LP3C) between March 2018 and December 2022. This cross-sectional study is based on the participants' baseline information. Long-term dietary information was collected through a validated food frequency questionnaire (FFQ), and colorectal polyps and adenomas were identified through electronic colonoscopy. Employing multivariate logistic regression, results were expressed as odds ratios (ORs) with their corresponding 95% confidence intervals (95% CIs). 4,942 cases of colorectal polyps and 2,678 cases of adenomas were ascertained. A significant positive association was found between total soy intake and the occurrence of polyps/adenomas. Considering cooking methods, a notable increase in polyp risk was associated with the consumption of fried soys while no association was detected for boiled or marinated soys. Furthermore, total soy intake demonstrated associations with large and multiple polyps, polyps Yamade-typed less than II, and polyps across all anatomical subsites. Within the high-risk CRC population in China, increased soy product intake was linked to a higher risk of polyps, primarily attributed to the consumption of fried soys. This suggests that modifying cooking methods to avoid fried soys may serve as a preventive strategy for colorectal polyps.

Reliability of large language models for advanced head and neck malignancies management: a comparison between ChatGPT 4 and Gemini Advanced

PurposeThis study evaluates the efficacy of two advanced Large Language Models (LLMs), OpenAI’s ChatGPT 4 and Google’s Gemini Advanced, in providing treatment recommendations for head and neck oncology cases. The aim is to assess their utility in supporting multidisciplinary oncological evaluations and decision-making processes.MethodsThis comparative analysis examined the responses of ChatGPT 4 and Gemini Advanced to five hypothetical cases of head and neck cancer, each representing a different anatomical subsite. The responses were evaluated against the latest National Comprehensive Cancer Network (NCCN) guidelines by two blinded panels using the total disagreement score (TDS) and the artificial intelligence performance instrument (AIPI). Statistical assessments were performed using the Wilcoxon signed-rank test and the Friedman test.ResultsBoth LLMs produced relevant treatment recommendations with ChatGPT 4 generally outperforming Gemini Advanced regarding adherence to guidelines and comprehensive treatment planning. ChatGPT 4 showed higher AIPI scores (median 3 [2–4]) compared to Gemini Advanced (median 2 [2–3]), indicating better overall performance. Notably, inconsistencies were observed in the management of induction chemotherapy and surgical decisions, such as neck dissection.ConclusionsWhile both LLMs demonstrated the potential to aid in the multidisciplinary management of head and neck oncology, discrepancies in certain critical areas highlight the need for further refinement. The study supports the growing role of AI in enhancing clinical decision-making but also emphasizes the necessity for continuous updates and validation against current clinical standards to integrate AI into healthcare practices fully.

Diabetes and gastric cancer incidence and mortality in the Asia Cohort Consortium: A pooled analysis of more than a half million participants.

Evidence suggests a possible link between diabetes and gastric cancer risk, but the findings remain inconclusive, with limited studies in the Asian population. We aimed to assess the impact of diabetes and diabetes duration on the development of gastric cancer overall, by anatomical and histological subtypes. A pooled analysis was conducted using 12 prospective studies included in the Asia Cohort Consortium. Among 558 981 participants (median age 52), after a median follow-up of 14.9 years and 10.5 years, 8556 incident primary gastric cancers and 8058 gastric cancer deaths occurred, respectively. Cox proportional hazard regression models were used to estimate study-specific hazard ratios (HRs) and 95% confidence intervals (CIs) and pooled using random-effects meta-analyses. Diabetes was associated with an increased incidence of overall gastric cancer (HR 1.15, 95% CI 1.06-1.25). The risk association did not differ significantly by sex (women vs men: HR 1.31, 95% CI 1.07-1.60 vs 1.12, 1.01-1.23), anatomical subsites (noncardia vs cardia: 1.14, 1.02-1.28 vs 1.17, 0.77-1.78) and histological subtypes (intestinal vs diffuse: 1.22, 1.02-1.46 vs 1.00, 0.62-1.61). Gastric cancer risk increased significantly during the first decade following diabetes diagnosis (HR 4.70, 95% CI 3.77-5.86), and decreased with time (nonlinear p < .01). Positive associations between diabetes and gastric cancer mortality were observed (HR 1.15, 95% CI 1.03-1.28) but attenuated after a 2-year time lag. Diabetes was associated with an increased gastric cancer incidence regardless of sex, anatomical subsite, or subtypes of gastric cancer. The risk of gastric cancer was particularly high during the first decade following diabetes diagnosis.

Prevalence of human papillomavirus in oral cancer in Asia: A systematic review and meta-analysis.

To determine the prevalence of human papillomavirus (HPV) in oral squamous cell carcinoma (OSCC) across Asian countries, focusing on South and Southeast Asia. A systematic search of four databases-MEDLINE/PubMed, EMBASE, Scopus, and ProQuest-was conducted to identify observational studies published between January 2013 and December 2023. The pooled prevalence of HPV was estimated using random-effects models, and subgroup analysis was performed to investigate the source of heterogeneity. A total of 77 studies were included, comprising 7289 OSCC cases from 11 countries. The pooled HPV prevalence in OSCC was 23.1% (95% CI 17.9-28.7, I2 = 96.7%). South Asia had the highest prevalence (27.1%), followed by East Asia (19.4%), and Southeast Asia (16.7%). Two subtypes were commonly reported: HPV-16 (9.1%) and HPV-18 (5.1%). Anatomical subsites, buccal mucosa (34.0%), and floor of the mouth (33.2%) had similar ranges of HPV prevalence. All studies exhibited a high degree of heterogeneity, with the OSCC location and risk of bias identified as potential sources of heterogeneity. Due to the high HPV prevalence in OSCC in Asia, HPV detection in routine pathology practice is recommended. Future studies should be conducted in multicentre settings using similar HPV detection methods and reporting detailed demographic and clinical information on oral sub-sites.

Clinicopathological characteristics and prognosis of Epstein-Barr virus-associated gastric cancer.

Epstein-Barr virus (EBV)-associated gastric cancer (EBVaGC) is a distinct molecular subtype of gastric cancer (GC). At present, the clinical characteristics and prognostic implications of EBV infection and the potential clinical benefits of immune checkpoint blockade in GC remain to be clarified. Hence, this study was designed to analyze the clinical and pathological characteristics of GC patients with varying EBV infection states and compare their overall survival (OS). A retrospective study was performed on 1031 consecutive GC patients who underwent gastrectomy at the Affiliated Hospital of Xuzhou Medical University from February 2018 to November 2022. EBV-encoded RNA (EBER) in situ hybridization (ISH) was used for EBV assessment, and immunohistochemical staining was used for evaluation of human epidermal growth factor receptor 2 (HER2), programmed death ligand 1 (PD-L1), and Ki67 expression. EBVaGC was defined as tumors with EBV positivity. In addition, EBV-negative GC (EBVnGC) patients were matched with EBVaGC patients based on seven clinicopathological parameters (age, gender, anatomic subsite, tumor size, Lauren classification, degree of differentiation, and tumor-node-metastasis [TNM] stage). The correlations of clinical features with HER2, PD-L1, and Ki67 expression were evaluated statistically. The survival of patients was assessed through medical records, telephone, or WeChat communication, and prognostic analysis was performed using the logrank test as well as univariable and multivariable regression analysis. Out of 1031 GC patients tested, 35 (3.4%) were diagnosed with EBVaGC. Notably, the EBVaGC group exhibited a distinct predominance of males and younger patients, significantly higher Ki67 and PD-L1 expression levels, and a lower prevalence of pericancerous nerve invasion than the EBVnGC group (P < 0.01). In the 35 EBVaGC cases, Ki67 expression was negatively correlated with age (P < 0.05), suggesting that a younger onset age was associated with higher Ki67 expression. In addition, PD-L1 expression was correlated with the degree of differentiation, T-stage, and clinical stage of the patient. Furthermore, PD-L1 expression was elevated in tumors with lower differentiation or at later stages (P < 0.05). Using univariate analysis, Ki67, PD-L1, and clinical stage were identified as significant factors influencing the overall survival (OS) of EBVaGC patients (P < 0.05). Moreover, multivariate survival analysis revealed that clinical stage and Ki67 expression were independent risk factors for the OS of the patients (P < 0.05), and the three-year OS rate of EBVaGC patients was 64.2%. EBV-ISH is a practical and valuable method to identify EBVaGC. Owing to its unique etiological, pathological, and clinical characteristics, patients with EBVaGC might benefit from immune checkpoint blockade therapy.

Family history and gastric cancer incidence and mortality in Asia: a pooled analysis of more than half a million participants

BackgroundThe family history of gastric cancer holds important implications for cancer surveillance and prevention, yet existing evidence predominantly comes from case–control studies. We aimed to investigate the association between family history of gastric cancer and gastric cancer risk overall and by various subtypes in Asians in a prospective study.MethodsWe included 12 prospective cohorts with 550,508 participants in the Asia Cohort Consortium. Cox proportional hazard regression was used to estimate study-specific adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) for the association between family history of gastric cancer and gastric cancer incidence and mortality, then pooled using random-effects meta-analyses. Stratified analyses were performed for the anatomical subsites and histological subtypes.ResultsDuring the mean follow-up of 15.6 years, 2258 incident gastric cancers and 5194 gastric cancer deaths occurred. The risk of incident gastric cancer was higher in individuals with a family history of gastric cancer (HR 1.44, 95% CI 1.32–1.58), similarly in males (1.44, 1.31–1.59) and females (1.45, 1.23–1.70). Family history of gastric cancer was associated with both cardia (HR 1.26, 95% CI 1.00–1.60) and non-cardia subsites (1.49, 1.35–1.65), and with intestinal- (1.48, 1.30–1.70) and diffuse-type (1.59, 1.35–1.87) gastric cancer incidence. Positive associations were also found for gastric cancer mortality (HR 1.30, 95% CI 1.19–1.41).ConclusionsIn this largest prospective study to date on family history and gastric cancer, a familial background of gastric cancer increased the risk of gastric cancer in the Asian population. Targeted education, screening, and intervention in these high-risk groups may reduce the burden of gastric cancer.

Abstract LB156: Targeting epigenetic activity of beta-catenin/CBP impedes oral cancer progression

Abstract Head and neck cancer is a complex malignancy with its major anatomical subsite, cancer of the oral cavity, ranking among the most deadly and disfiguring cancers. Oral cancer presents primarily as HPV-negative oral squamous cell carcinoma (OSCC) whose etiology is associated with tobacco and alcohol use and for which there are limited treatments. Whereas immunotherapies, such as anti-PD-1 antibodies, have become a promising therapeutic option, only ~20% of head neck cancer patients benefit from anti-PD-1 immunotherapy. We and others have shown that non-mutational epigenetic reprogramming mediated by the β-catenin/CBP complex promotes aggressive cell phenotypes in OSCC by establishing open chromatin at the transcription start sites of genes associated with cancer stemness. Accordingly, pharmacological inhibition of this complex dramatically inhibits OSCC evolution in a syngeneic mouse model of OSCC. Here, we evaluated whether the inhibition of β-catenin/CBP epigenetic activity would enhance the effects of anti-PD-1 immunotherapy. We adapted a syngeneic mouse model of tobacco-associated oral carcinogenesis that utilizes a mouse cell line, 4MOSC1, derived from 4-nitroquinoline-1 oxide- (4NQO)-induced tongue tumors of C57BL/6J mice. After tumors developed for 7 days, mice were blindly separated into treatment cohorts (n=13, each) to receive vehicle control (PBS), monotherapy (either 10 mg/kg anti-PD-1 EOD IP, or 100 mg/kg E7386, a Wnt signaling pathway modulator, QD oral gavage) or combination therapy (anti-PD-1 + E7386). Tumor isografts were harvested 11 days post initiation of treatments and processed for histopathology, immunohistochemistry, and immunofluorescence analyses. Measurements of tumor volumes showed that combination therapy resulted in a statistically significant reduction by ~80% compared to control mice and that it surpassed tumor decrease by either monotherapy. These results were confirmed by histopathology analyses. Evaluation of tumor tissues by immunofluorescence revealed statistically significant decreases in Cbp, H3K4me3, Keratin 14, and Podoplanin expression in response to E7386 alone and in combination with anti PD-1. Collectively our results suggest that a combination therapy comprising anti PD-1 treatment with E7386-targeting β-catenin/CBP epigenetic signaling is likely to impede OSCC evolution to advanced disease. Supported by Eisai, Co Ltd Research Award (MAK), NIH 5R01 DE030350 (MAK, SM, XV) and 5R01 DE031413 (MVB). Citation Format: Emily Fisher, Anthony Spinella, Junji Matsui, Kenichi Nomoto, Xaralabos Varelas, Manish Bais, Maria Kukuruzinska. Targeting epigenetic activity of beta-catenin/CBP impedes oral cancer progression [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 2 (Late-Breaking, Clinical Trial, and Invited Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(7_Suppl):Abstract nr LB156.

Systemic Bevacizumab for Recurrent Respiratory Papillomatosis: A Single Institution's Experience.

Medical therapies to limit disease recurrence are critically needed for recurrent respiratory papillomatosis (RRP). Systemic bevacizumab is emerging as an exciting adjuvant therapy toward this end, but uptake has been poor due to the lack of experience and awareness of best prescribing practices. The objective of this study was to describe a single tertiary care academic medical center's experience using systemic bevacizumab for the treatment of RRP. A retrospective review was performed to identify patients with RRP on systemic bevacizumab. Demographic and clinical characteristics, findings on imaging reports, and disease response at all anatomic subsites involved in papilloma were documented. Of the 17 RRP patients on systemic bevacizumab, 9 (52.9%) were male, and 12 (70.6%) were diagnosed with juvenile-onset RRP. The total lifetime number of surgeries was high, with more than half (n = 9; 52.9%) undergoing more than 50 surgeries. Following induction of systemic bevacizumab, a significant reduction in patients with laryngeal (n = 15; 94.1% vs. n = 7; 41.2%, p < 0.001) and tracheal (n = 11; 64.7% vs. n = 5; 29.4%, p = 0.04) RRP was noted. Surgical frequency was significantly lower following systemic bevacizumab (2.5 vs. 0.5 surgeries per year; p < 0.001). The most common complications were new-onset hypertension (n = 4; 23.5%) and proteinuria (n = 5; 29.4%). Systemic bevacizumab is effective in reducing the number of surgeries needed for RRP while exhibiting a relatively safe complication profile. Papillomas in the larynx and trachea are most responsive to systemic bevacizumab, while pulmonary RRP is most likely to exhibit a partial-to-stable response. 4 Laryngoscope, 134:3253-3259, 2024.

Abstract 6613: Understanding the causes of head and neck cancer using mutational signature analysis

Abstract The geographical incidence of head and neck cancer (HNC) is heterogeneous, reflecting the prevalence of its main risk factors. Tobacco, either alone or combined with alcohol, is the predominant cause of HNC, while the potential of alcohol as an independent carcinogen is uncertain. Moreover, the etiology remains unknown for ~28% of cases. In this study, we used mutational signature analysis to 1) track the exposure to known and putative risk factors for HNC across multiple geographical regions and subsites, 2) evaluate whether an alcohol signature is present in HNC, and 3) assess its interaction with tobacco or other risk factors. Whole-genome sequencing data was generated from 265 HNC cases from retrospective HNC studies in Europe and South America with available lifestyle and environmental exposure data. Mutational and copy number (CN) signatures were extracted with SigProfilerExtractor and decomposed into COSMIC reference signatures. Associations between the mutational signatures and epidemiological or molecular data were assessed using multivariate regression analysis. The analysis revealed known and previously unreported signatures of endogenous and exogenous exposures. APOBEC-driven signatures (SBS2, SBS13) were identified in 97% (258/265) of cases. We observed differences in tobacco-related mutagenesis across anatomical subsites. While known tobacco signatures (SBS4, SBS92, DBS2, and ID3) were found in larynx cases, the novel signature SBS1536I was enriched in oral cavity cases from ever-smokers, which suggests a site-specific mutagenic effect from different tobacco carcinogens. Furthermore, we demonstrate that signatures associated with alcohol consumption (SBS16, DBS4, and ID11) were enriched in cases exposed to both tobacco and alcohol, indicating an interaction between the two. We also extracted signatures indicative of ultraviolet (UV) light exposure (SBS7a-c, DBS1, and ID13) in cases from the inner lip, tongue, and floor of the mouth, implying a role of UV exposure in oral cavity carcinogenesis. Finally, hierarchical clustering analysis revealed three distinct CN profiles in HNC, each linked to different risk factors and driver mutations: 1) A CN-rich polyploid cluster associated with tobacco smoking and CN signatures of chromosomal instability, including one novel signature (CN48G) enriched in samples from South America, 2) a CN-rich diploid cluster comprising cases related to both tobacco and human papillomavirus infection; and 3) a CN-neutral cluster enriched in samples with unknown etiology. This study uncovers APOBEC signaling, tobacco, alcohol, and potentially UV light exposure, as potent mutagenic agents in HNC. Our findings suggest that the mutational impact of tobacco in HNC is tissue-specific, and that tobacco may enhance the oncogenic effects of alcohol. Finally, the CN profile in HNC is strongly influenced by exposure to risk factors and driver mutations in the tumors. Citation Format: Laura Torrens, Sarah Moody, Carol De Carvalho, Sergey Senkin, Saamin Cheema, Mariya Kazachkova, Valerie Gaborieau, Behnoush Abedi-Ardekani, Ricardo Cortez Cardoso Penha, Joshua Atkins, Priscilia Chopard, Jingwei Wang, Stephen Fitzgerald, Calli Latimer, Christine Carreira, Thomas Cattiaux, Marcos Diaz-Gay, Laura Humphreys, Ludmil B. Alexandrov, Michael R. Stratton, Sandra Perdomo, Paul Brennan, HEADSpAcE consortium. Understanding the causes of head and neck cancer using mutational signature analysis [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 6613.

Lymphatic drainage of sinonasal malignancies and the role of sentinel node biopsies

BackgroundLocoregional recurrence is a critical factor in the prognosis of sinonasal malignancies. Due to the rarity of these tumours, as well as the heterogeneity of histologies and anatomical subsites, there is little evidence regarding the rate and location of regional metastases in sinonasal malignancies. Elective regional lymph node dissection in the therapy of sinonasal malignancies has become controversial. On the one hand, elective regional lymph node dissection is considered to be an overtreatment in the cN0 cases. On the other hand, undetected occult lymphatic metastases are associated with a poor prognosis. In this study, we discuss the role of sentinel lymph node biopsy as a minimally invasive procedure in the treatment of sinonasal malignancies based on our two years of practical experience and the currently available data.ResultsThis is a descriptive, monocentric, retrospective study, including 20 cases of cN0 malignant sinonasal neoplasm, that underwent a surgical therapy between 2020 and 2022. The following aspects were investigated: tumour entity, localisation of the primary tumour, tumoral stage, localisation of the sentinel lymph nodes, and postoperative complications. Squamous cell carcinoma was the most frequently diagnosed tumour entity (50%), followed by adenocarcinoma (20%) and malignant melanoma (15%), adenoid cystic carcinoma and mucoepidermoid carcinoma. Sentinel lymph nodes were most frequently found in the ipsilateral neck region I (45%), followed by the ipsilateral neck region II (40%). In all cases, the removed lymph nodes were free of malignancy. There were no postoperative complications due to lymph node biopsy. There were no recurrences during the study period.ConclusionSentinel node biopsy could add more safety to the management of cN0 sinonasal malignancies due to its low morbidity. Whether SNB could provide an alternative to elective neck dissection in the management of SNM should be investigated in further studies.

Similarity Network Analysis of the Adaptive Immune Response in the Proximal Airway.

Recent immunologic study of the adaptive immune repertoire in the subglottic airway demonstrated high-frequency T cell clones that do not overlap between individuals. However, the anatomic distribution and antigenic target of the T cell repertoire in the proximal airway mucosa remain unresolved. Single-cell RNA sequencing of matched scar and unaffected mucosa from idiopathic subglottic stenosis patients (iSGS, n = 32) was performed and compared with airway mucosa from healthy controls (n = 10). T cell receptor (TCR) sequences were interrogated via similarity network analysis to explore antigenic targets using the published algorithm: Grouping of Lymphocyte Interactions by Paratope Hotspots (GLIPH2). The mucosal T cell repertoire in healthy control airways consisted of highly expressed T cell clones conserved across anatomic subsites (trachea, bronchi, bronchioles, and lung). In iSGS, high-frequency clones were equally represented in both scar and adjacent non-scar tissue. Significant differences in repertoire structure between iSGS scar and unaffected mucosa was observed, driven by unique low-frequency clones. GLIPH2 results suggest low-frequency clones share targets between multiple iSGS patients. Healthy airway mucosa has a highly conserved T cell repertoire across multiple anatomic subsites. Similarly, iSGS patients have highly expressed T cell clones present in both scar and unaffected mucosa. iSGS airway scar possesses an abundance of less highly expanded clones with predicted antigen targets shared between patients. Interrogation of these shared motifs suggests abundant adaptive immunity to viral targets in iSGS airway scar. These results provide insight into disease pathogenesis and illuminate new treatment strategies in iSGS. NA Laryngoscope, 134:3245-3252, 2024.

Posttreatment Head and Neck Cancer Imaging: Anatomic Considerations Based on Cancer Subsites.

Posttreatment imaging surveillance of head and neck cancer is challenging owing to complex anatomic subsites and diverse treatment modalities. Early detection of residual disease or recurrence through surveillance imaging is crucial for devising optimal treatment strategies. Posttreatment imaging surveillance is performed using CT, fluorine 18-fluorodeoxyglucose PET/CT, and MRI. Radiologists should be familiar with postoperative imaging findings that can vary depending on surgical procedures and reconstruction methods that are used, which is dictated by the primary subsite and extent of the tumor. Morphologic changes in normal structures or denervation of muscles within the musculocutaneous flap may mimic recurrent tumors. Recurrence is more likely to occur at the resection margin, margin of the reconstructed flap, and deep sites that are difficult to access surgically. Radiation therapy also has a varying dose distribution depending on the primary site, resulting in various posttreatment changes. Normal tissues are affected by radiation, with edema and inflammation occurring in the early stages and fibrosis in the late stages. Distinguishing scar tissue from residual tumor becomes necessary, as radiation therapy may leave behind residual scar tissue. Local recurrence should be carefully evaluated within areas where these postradiation changes occur. Head and Neck Imaging Reporting and Data System (NI-RADS) is a standardized reporting and risk classification system with guidance for subsequent management. Familiarity with NI-RADS has implications for establishing surveillance protocols, interpreting posttreatment images, and management decisions. Knowledge of posttreatment imaging characteristics of each subsite of head and neck cancers and the areas prone to recurrence empowers radiologists to detect recurrences at early stages. ©RSNA, 2024 Test Your Knowledge questions in the supplemental material and the slide presentation from the RSNA Annual Meeting are available for this article.

Avocado and Guacamole Consumption and Colorectal Cancer Risk: The Multiethnic Cohort Study

Dietary fiber and phytonutrients can protect against colorectal cancer, yet their consumption is low in the US. Avocados are a potential source of these beneficial nutrients. Therefore, this study aimed to examine the relationship between avocados/guacamole consumption and colorectal cancer risk in the Multiethnic Cohort Study. We assessed avocados/guacamole consumption by using a food frequency questionnaire. We classified participants into three consumer groups: <1 serving/month, 1–3 servings/month, and ≥1 serving/week with one serving defined as ½ avocado or ½ cup. Colorectal cancer cases were ascertained through the Surveillance, Epidemiology and End Results Program cancer registries. Cox proportional hazards models of colorectal cancer were used to calculate hazard ratios and 95% confidence intervals across avocados/guacamole intake groups in each sex overall and by anatomic subsite (i.e., right colon, left colon, and rectum) and race and ethnicity. Of 192,651 eligible participants, 62.8% reported consuming <1 serving/month avocados/guacamole, 26.7% reported 1–3 servings/month, and 10.5% reported ≥1 serving/week. When adjusted for relevant covariates, there was no significant association with incident colorectal cancer overall, for subsites, or within racial and ethnic subgroups (all p for trend ≥ 0.06). In this large prospective cohort study, we did not find that consumption of avocados/guacamole was associated with colorectal cancer risk.