Anatomic Subsite Research Articles

The prognostic value of machine learning techniques versus cox regression model for head and neck cancer.

Accurate prognostic prediction for head and neck cancer (HNC) is important for the improvement of clinical management. We aimed to compare the prognostic value of various machine learning techniques (MLTs) and statistical Cox regression model for different types of HNC. Clinical data of HNC patients were extracted from the Surveillance, Epidemiology, and End Results (SEER) database from 1974 to 2016. The prediction performance of five ML models, including random forest (RF), gradient boosting decision tree (GBDT), support vector machine (SVM), neural network (NN) and deep learning (DL), were compared with the statistical Cox regression model by estimating the concordance index (C-index), integrated Brier score (IBS), time-dependent receiver operating characteristic (ROC) curve and the area under the curve (AUC). Our results showed that the RF model outperformed all other models in prognostic prediction for all tumor sites of HNC, particularly for major salivary gland cancer (MSGC, C-index: 88.730±0.8700, IBS: 7.680±0.4800), oral cavity cancer (OCC, C-index: 84.250±0.6700, IBS: 11.480±0.3300) and oropharyngeal cancer (OPC, C-index: 82.510±0.5400, IBS: 10.120±0.1400). Meanwhile, we analyzed the importance of each clinical variable in the RF model, in which age and tumor size presented the strongest positive prognostic effects. Additionally, similar results can be observed in the internal (6th edition of the AJCC TNM staging system cohort) and external validations (the TCGA HNC cohort). The RF model is a promising prognostic prediction tool for HNC patients, regardless of the anatomic subsites.

Associations between cigarette smoking and biliary tract cancer by anatomic subsite and sex: a prospective cohort study in Japan

PurposeBiliary tract cancer (BTC) has not been considered a tobacco-related cancer, largely because of inconclusive results from epidemiological studies. We herein evaluate the association between cigarette smoking and risk of death from BTC by anatomic subsite and sex using data from a large, prospective cohort study in Japan.MethodsThe present study included 97,030 Japanese individuals who were enrolled in 1988–1990 and followed until 31 December 2009. Cox proportional hazards regression models were used to estimate relative risks (RRs) and 95% confidence intervals (CIs) for the association of BTC with cigarette smoking, including smoking status, number of cigarettes smoked per day, and pack-years of smoking.ResultsDuring a mean follow-up of 16.2 years, we documented 484 deaths (187 from gallbladder cancers and 297 from cancers of other and unspecified biliary tract parts). After adjustment for sex, age, body mass index, alcohol consumption, and history of gallstones, current smokers had a higher risk of death due to BTC (RR = 1.35, 95% CI = 1.01–1.79) than never smokers. In the analyses by anatomic subsite, current smoking was associated with an increased risk of death from gallbladder cancer (RR = 1.89 95% CI = 1.19–3.02), whereas no evidence of an association was noted for cancers of other and unspecified biliary tract parts (RR = 1.10, 95% CI = 0.77–1.58). Moreover, mortality risk increased with an increasing number of cigarettes smoked per day and pack-years of smoking, particularly for gallbladder cancer in men.ConclusionCigarette smoking is associated with an increased risk of death from BTC, particularly gallbladder cancer, in Japanese men.

Associations of cigarette smoking, alcohol drinking and body mass index with survival after colorectal cancer diagnosis by anatomic subsite: a prospective patient cohort study in Japan.

Cigarette smoking, alcohol drinking and obesity are known to be risk factors for colorectal cancer. These factors may affect survival after diagnosis, but evidence has been inconsistent. We investigated subsite-specific associations between prediagnosis smoking, alcohol drinking and body mass index and survival in colorectal cancer. Subjects were 1300 patients (colon 778; rectum 502; concurrent 20) with histologically confirmed colorectal cancer diagnosed during 1997-2013 at a single institution in Japan. Histories of smoking and alcohol drinking, height and prediagnosis weight were assessed using a self-administered questionnaire. Using Cox proportional hazards model, hazard ratios and 95% confidence intervals of mortality were estimated. During a median follow-up period of 6.7years, 479 deaths were documented. Ever-smoking was associated with an increased risk of all-cause death among patients with colon cancer (hazard ratio: 1.47; 95% confidence interval: 1.07-2.02 compared with never-smoking). According to colon subsite, this increased risk was clear in patients with proximal colon cancer (hazard ratio: 2.09; 95% confidence interval: 1.28-3.40). There was no association between smoking and rectal cancer survival. Alcohol drinking was not associated with survival for either colon or rectal cancer. Among patients with rectal cancer, higher body mass index was associated with a lower risk of all-cause (Ptrend=0.0006) and disease-specific death (Ptrend=0.02). For colon cancer, lower body mass index tended to be associated with a higher risk of all-cause death (Ptrend=0.05). The results indicate that lifestyles identified as risk factors for colorectal cancer may impact differently on patient survival according to anatomic subsite.

Distinct sociodemographic differences in incidence and survival rates for human papillomavirus (HPV)-like, non-HPV-like, and "other"-like oral cavity and pharynx cancers: An analysis of Surveillance, Epidemiology and End Results (SEER) Program data.

PurposeOral cavity and pharynx cancer (OCPC) cases are traditionally dichotomized into human papillomavirus (HPV) and non-HPV types. Using a proxy for HPV status, the objective was to evaluate differences in incidence and survival rates of OCPC anatomic sub-sites identified as: 1) HPV-like; 2) non-HPV-like (i.e., tobacco/alcohol-related); and 3) “other”-like (i.e., not predominantly HPV-like nor tobacco/alcohol-like) OCPCs.MethodsData from the Surveillance, Epidemiology and End Results Program were used to examine incidence and survival rates for OCPC categories over time and according to age, sex, race, ethnicity, stage at diagnosis, neighborhood socioeconomic status (i.e., nSES or Yost Index), and rurality/urbanity (i.e., Rural Urban Commuting Area (RUCA) codes). Although HPV status was unavailable in this dataset, OCPC anatomies and histologies were classified into three sub-categories, based on potential risk factors. Frequencies, average annual, age-adjusted incidence rates, five-year relative survival rates, and 95% confidence intervals were examined across and within OCPC categories.ResultsHPV-like OCPC incidence rates sharply increased from 1975 through 2015 while non-HPV-like and “other”-like OCPC rates decreased, all converging to similar rates from 2016 through 2018. Increasing over time for both categories, survival was highest for HPV-like and lowest for non-HPV-like OCPCs; survival for “other”-like OCPCs remained stable. Generally, across OCPC categories, incidence and survival rates were significantly higher among males vs. females, Whites vs. African Americans, and non-Hispanics vs. Hispanics. “Other”-like OCPC incidence decreased with increasing nSES tertiles, while no nSES differences were observed for HPV-like and non-HPV-like OCPCs. Incidence rates were significantly lower among urban (vs. rural) residents. For all OCPC categories, survival rates were significantly higher with increasing nSES and variable across RUCA categories.Conclusion/ImpactHPV-like and non-HPV-like OCPC cases had distinct sociodemographic differences; “other”-like OCPC cases were a sociodemographic blend of HPV-like and non-HPV-like OCPC cases, resembling more of the sociodemographic makeup of non-HPV-like OCPC cases. To prevent new OCPCs, additional studies are needed to epidemiologically and clinically differentiate between OCPC categories so that high-risk groups can be better targeted in future public health interventions.

Assessment of neoadjuvant chemotherapy with docetaxel, cisplatin, and fluorouracil in patients with oral cavity cancer.

Chemotherapy with docetaxel, cisplatin, and fluorouracil (TPF) has been studied in patients with head and neck cancer. Its impact on patients with oral cavity cancer was not specified. We consecutively reviewed medical files of patients with untreated oral cavity cancer who received neoadjuvant TPF chemotherapy in our department from January 2017 to April 2020. Outcomes included the objective response to TPF chemotherapy, factors associated with the response, and progression and survival in different response groups. A total of 167 patients were included, with half of stage IV disease. Complete or partial response was observed in 51 patients. A total of 91 patients had stable disease, and 25 patients had progressive disease. The response was not associated with age, sex, anatomic subsite, and the tumor's T stage. It was related with N stage (p < 0.001) and clinical stage (p=0.004). Most patients with bulky nodes or nodes with obvious necrosis showed low response or even progressed after neoadjuvant TPF chemotherapy. The planned surgery was conducted in 159 patients. Disease relapse mostly occurred in 2 years after treatment. The 2-year overall survival and the progression-free survival were 89.0% and 85.2% for patients with complete or partial response, 62.4% and 55.6% for patients with stable disease, and 12.5% and 4.2% for patients with progressive disease, respectively. The response of neoadjuvant TPF chemotherapy in patients with oral cavity cancer is related to disease stage, especially the nodal stage. Patients with complete or partial response developed less progression events and better survival.

Typical and Atypical Symptoms of Petrous Apex Cholesterol Granuloma: Association with Radiological Findings.

Objective: Petrous apex cholesterol granuloma (PACG) is a lesion that can give rise to different symptoms, and correlations with etiopathology are ambiguous. The aim of this study is to analyze the association between PACG symptoms and radiological findings at presentation, in order to establish a reproduceable pre-operative radiological evaluation and guide the surgical indication. Methods: PACG patients were collected in two tertiary care hospitals. All cases underwent CT/MRI to evaluate the cyst localization and erosion of surrounding structures. Typical and atypical symptoms were then analyzed and compared to radiologic findings established in accordance with the literature. Results: Twenty-nine patients were recruited; the most common symptoms were headache (69%), diplopia (20.7%) and fainting (24.1%), an atypical clinical manifestation related to jugular tubercle involvement. Significant associations between symptoms and radiologic findings were noted in terms of headache and temporal lobe compression (p = 0.04), fainting and jugular tubercle erosion (p < 0.001), vestibular symptoms and internal auditory canal erosion (p = 0.02), facial paresthesia and Meckel’s cave compression (p = 0.03), diplopia and Dorello canal involvement (p = 0.001), and tinnitus and cochlear basal turn erosion (p < 0.001). All patients were treated via an endoscopic–endonasal approach, in which extension was tailored to each case. At a median follow-up of 46 months, 93.1% of patients experienced resolution of symptoms. Conclusions: This clinico-radiological series demonstrates associations between symptoms and anatomical subsites involved with PACG. Hence, it may guide the surgeon at the time of surgical decision, since it asserts that typical and atypical symptoms are actually related to PACG.

Reconstruction of oral cavity defects using myogenous-only scapular tip free-flaps.

BackgroundOral cavity reconstruction is very challenging anatomical subsite to reconstruct. Large defects often require free tissue reconstruction to provide the best chance of form and function. Additionally, free tissue reconstruction aids to prevent fistula formation. We aimed to determine outcomes of oral cavity defect reconstruction using scapular tip free flaps with a myogenous intraoral component.MethodsAll patients with a mandibular or maxillary bony defect that included a disruption of the intraoral mucosa component between 07/1/14 and 07/31/17. Patients were reconstructed with a scapular tip free flap, which included a muscular component that was used to recreate the oral mucosa. The primary study outcomes were flap success rates, development of orocutaneous or oronasal fistula, rate of resuming oral diet as well as the occurrence of medical and surgical complications in the first month following surgery. The tested hypothesis was formulated before data collection began.ResultsTwenty‐five patients were identified by the study criteria. There was one (4%) flap that failed, while orocutaneous fistula occurred in two patients (8%). Prior history of osteoradionecrosis was a statistically significant predictor of overall complication (p < .05).ConclusionsIntraoral myogenous reconstruction allows for re‐mucosalization of the oral cavity defect and is associated with high viability and low‐complication rates. In patients with amenable oral mucosal defects, a myogenous scapular tip free flap is a suitable reconstructive option.

Inverse Association between Dietary Iron Intake and Gastric Cancer: A Pooled Analysis of Case-Control Studies of the Stop Consortium.

Background: Inconsistent findings have been reported regarding the relationship between dietary iron intake and the risk of gastric cancer (GC). Methods: We pooled data from 11 case-control studies from the Stomach Cancer Pooling (StoP) Project. Total dietary iron intake was derived from food frequency questionnaires combined with national nutritional tables. We derived the odds ratios (ORs) and 95% confidence intervals (CIs) for quartiles of dietary iron through multivariable unconditional logistic regression models. Secondary analyses stratified by sex, smoking status, caloric intake, anatomical subsite and histological type were performed. Results: Among 4658 cases and 12247 controls, dietary iron intake was inversely associated with GC (per quartile OR 0.88; 95% CI: 0.83–0.93). Results were similar between cardia (OR = 0.85, 95% CI = 0.77–0.94) and non-cardia GC (OR = 0.87, 95% CI = 0.81–0.94), and for diffuse (OR = 0.79, 95% CI = 0.69–0.89) and intestinal type (OR = 0.88, 95% CI = 0.79–0.98). Iron intake exerted an independent effect from that of smoking and salt intake. Additional adjustment by meat and fruit/vegetable intake did not alter the results. Conclusions: Dietary iron is inversely related to GC, with no difference by subsite or histological type. While the results should be interpreted with caution, they provide evidence against a direct effect of iron in gastric carcinogenesis.

Use of anti-androgenic 5α-reductase inhibitors and risk of oesophageal and gastric cancer by histological type and anatomical sub-site

BackgroundTo investigate if anti-androgenic medications 5α-reductase inhibitors (5-ARIs) decrease the risk of developing oesophageal and gastric tumours, analysed by histological type and anatomical sub-site.MethodsA Swedish population-based cohort study between 2005 and 2018 where men using 5-ARIs were considered exposed. For each exposed participant, ten male age-matched non-users of 5-ARIs (non-exposed) were included. Multivariable Cox regression provided hazard ratios (HR) with 95% confidence intervals (CI) adjusted for age, calendar year, smoking, non-steroidal anti-inflammatory drugs/aspirin use, and statins use. Further adjustments were made depending on the tumour analysed.ResultsThe cohort included 191,156 users of 5-ARIs and 1,911,560 non-users. Overall, the use of 5-ARIs was not associated with any statistically significantly reduced risk of oesophageal or cardia adenocarcinoma (adjusted HR 0.92, 95% CI 0.82–1.02) or gastric non-cardia adenocarcinoma (adjusted HR 0.90, 95% CI 0.80–1.02). However, the use of 5-ARIs indicated a decreased risk of oesophageal or cardia adenocarcinoma among obese or diabetic participants (adjusted HR 0.55, 95% CI 0.39–0.80) and a reduced risk of oesophageal squamous cell carcinoma (adjusted HR 0.49, 95% CI 0.37–0.65).ConclusionUsers of 5-ARIs may have a decreased risk of developing oesophageal or cardia adenocarcinoma among those obese or diabetic, and a decreased risk of oesophageal squamous cell carcinoma.

Human Papillomavirus and Risk of Head and Neck Squamous Cell Carcinoma in Iran.

ABSTRACTHuman papillomavirus (HPV) causes a subset of head and neck squamous cell carcinoma (HNSCC). Knowledge of determinants of α-, β-, and γ-HPVs types in the oral cavity is required for a better understanding of HNSCC development. Oral rinse samples of 498 HNSCC cases and 242 controls from the IROPICAN study—a large multicenter case-control study in Iran—were screened for 21 α-HPV, 46 β-HPVs, and 52 γ-HPVs using bead-based HPV genotyping assays. α-HPVs were detected only in 1.2% of the patients and 2.9% of the controls from which HPV16 was the most prevalent type among participants. β-HPVs were detected in 43.8% of the patients and 38.6% of the controls where the lip and oral cavity (45.5%) had the highest positivity. Values for γ-HPV prevalence in patients and controls were 26.1% and 24.7%, respectively. The highest percentage of γ-HPV positivity was found in the larynx (30.4%). Concerning the β genus, HPV23 and HPV38 were the most prevalent types among the patients and controls, respectively. For the γ genus, SD2 in cases and HPV134 in controls were the most prevalent types. Overall, detection of α-HPVs (aOR, 0.40; 95% CI = 0.1 to 1.2; P = 0.11), β-HPVs (aOR, 1.9; 95% CI = 0.9 to 1.6; P = 0.29), and γ-HPVs infections (aOR, 1.04; 95% CI = 0.7 to 1.5; P = 0.83) was not associated with the HNSCC development. Our data did not suggest an HPV-related etiology for HNSCC pathogenesis. Nonetheless, this study provides novel insights into the diversity of β-, and γ-HPVs in different HNSCC anatomical subsites.IMPORTANCE Infection with human papillomavirus (HPV) is responsible for a subset of neck squamous cell carcinoma (HNSCC), but knowledge of the prevalence of and risk factors for oral HPV infection, especially cutaneous types in Iran, remains unknown. In a large retrospective study, the authors used a sensitive assay for the detection of α-, β-, and γ-HPVs in oral rinse samples of HNSCC and matched controls. They find that the α-HPV contribution to HNSCC in Iran is lower than global prevalence. High-risk α-HPVs or cutaneous β- and γ-HPVs were not associated with the HNSCC development. Besides, this study provides novel insights into the diversity of β- and γ-HPVs in different HNSCC anatomical subsites.

Abstract 2142: Prognostic and predictive applications from mesenchymal gene expression subtype analysis for early-stage, HPV(-) head and neck squamous cell carcinoma

Abstract Introduction: Although often presented as one disease for genomic studies, head and neck squamous cell carcinoma (HNSCC) is treated according to clinical factors such as anatomic subsite, and tumor stage. Oral cavity squamous cell carcinoma (OCSCC) comprises 1/3 of all HNSCC and is predominantly HPV(-). Depending upon clinical stage, OCSCC treatment involves surgical resection +/- neck dissection, followed by radiation +/- chemotherapy. Our group and others previously described four mRNA expression patterns (classical, atypical, basal, and mesenchymal), each with unique genomic features and prognosis. Here, we further examine the clinical utility of gene expression subtyping in HNSCC and introduce the potential for predictive applications in HPV(-) HNSCC according to clinically relevant subgroups including oral cavity cancer. Experimental Procedures: Multiple independent HNSCC datasets were obtained from public repositories, totaling 562 patients, including from MD Andersen (MDA) (GSE41117) and the Cancer Genome Atlas (TCGA) sourced from the Genome Data Commons. Cases were included for further analysis if they had N stage and overall survival values. Samples were assigned molecular subtypes (basal, mesenchymal, atypical or classical) using a reduced gene set version of the classifier reported earlier. HPV status was determined by HPV gene expression. The clinical endpoint was overall survival at censured at 36 months. Kaplan-Meier (KM) plots and logrank tests were used to investigate associations between clinical variables and survival. Cox models were used to adjust for potential confounders. All statistics were performed using the survival package in R. Results: Of the 418 training patients from the TCGA dataset that met analysis criteria, nearly 20% presented with stage I and II tumors. In the clinically relevant subgroup of node(-) OCSCC patients, mesenchymal subtype was associated with worse survival (HR 2.4, p=0.021), offering a novel and potentially actionable biomarker in otherwise early-stage and low risk disease. Associations in the MDA validation cohort confirmed the association. Node(-) non-mesenchymal OCSCC patients had far better survival (no deaths observed) compared to node(-) mesenchymal and all node(+) patients which had similarly poor survival. Differential responses as a function of radiation will be presented. Summary and Conclusions: This study confirms that the mesenchymal subtype is associated with worse outcomes across all cases of HNSCC. However, we demonstrate that mesenchymal subtype is associated with poor survival, even in the clinically relevant setting of early-stage, node(-) OCSCC treated with surgical resection. These findings highlight the potential value of gene expression subtyping as an adjunct to pathology for deciding which treatment option is best suited for patients with HNSCC. Citation Format: D. Neil Neil Hayes, MD, MS, MPH, Greg Mayhew, Josh Uronis, Jose Zevallos. Prognostic and predictive applications from mesenchymal gene expression subtype analysis for early-stage, HPV(-) head and neck squamous cell carcinoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 2142.

Trends in the incidence of early-onset invasive colorectal cancer between 1990 and 2018, stratified by race/ethnicity, gender, and anatomic sub-sites among Pennsylvania residents.

10543 Background: Recent data report a rising incidence of colorectal cancer in the younger population and epidemiological evidence is useful to enable clinicians understand evolving trends and better counsel patients on the potential risks/benefits of early screening. We explored the trends in incidence of early-onset invasive colorectal cancer by race/ethnicity, gender, and anatomic sub-sites. Methods: Repeated cross-sectional analyses were conducted among adults &lt; 50 years diagnosed with invasive colorectal cancer between 1990-2018 in Pennsylvania using data from the Pennsylvania Department of Health Cancer Registry. Temporal trends in invasive cancer with age adjusted incidence rates according to race/ethnicity, gender, and anatomical sub-sites were assessed using the Enterprise Data Dissemination Informatics Exchange (EDDIE). Results: 16,154 cases of early-onset invasive colorectal cancer were diagnosed between 1990 and 2018. There was an increased incidence of invasive colorectal cancer in the general population especially when stratified by gender, race/ethnicity and among those &lt; 40 years of age. While rates among Whites nearly doubled from 5.4 per 100,000 (95% Confidence Interval (CI): 4.9–6.0 per 100,000) population to 9.0 per 100,000 (95% CI: 8.2– 9.7 per 100,000) population, the rates in the Black population have been decreasing in recent years from a peak of 10.4 per 100,000 (95% CI: 8.4–12.7 per 100,000) population in 2011 to 7.3 per 100,000 (95% CI: 5.7–9.3 per 100,000) population in 2018. However, the Hispanic rates have remained stable. Across anatomical subsites, the rectum, rectosigmoid and sigmoid colon were found to have rising trends in incidence rates over time. Conclusions: There is increased awareness on the need for early diagnosis of colorectal cancer in the young Black population. However, we found trends toward increasing incidence rates among Whites while rates in the Black population are now decreasing. These findings accentuate the need for quality provider-patient communication during primary care visits with a goal to improve adherence to the new colorectal cancer screening guidelines regardless of race/ethnicity.

SO-24 Young age as bad prognosis of colorectal cancer: An earlier screening needed?

Diagnosis of colorectal cancer (CRC) at an early age has become a challenging trend for oncology worldwide, besides increased mortality in this population has emerged over the last decade. Several features of bad prognosis as an anatomic subsite, stage at diagnosis, race, and ethnicity have been studied for young adults (< 30 years old) with CRC. Nevertheless, their correlation to a bad prognosis remains unclear. This study aimed to describe the clinicopathological features and their impact on the overall survival of young Mexican adults diagnosed with CRC treated in the National Cancer Institute.

Sugar-sweetened beverage and sugar consumption and colorectal cancer incidence and mortality according to anatomic subsite

Recent preclinical research strongly suggests that dietary sugars can enhance colorectal tumorigenesis by direct action, particularly in the proximal colon that unabsorbed fructose reaches. We aimed to examine long-term consumption of sugar-sweetened beverages (SSBs) and total fructose in relation to incidence and mortality of colorectal cancer (CRC) by anatomic subsite. We followed 121,111 participants from 2 prospective US cohort studies, the Nurses' Health Study (1984-2014) and Health Professionals Follow-Up Study (1986-2014), for incident CRC and related death. Cox proportional hazards regression was used to compute HRs and 95% CIs. During follow-up, we documented 2733 incident cases of CRC with a known anatomic location, of whom 901 died from CRC. Positive associations of SSB and total fructose intakes with cancer incidence and mortality were observed in the proximal colon but not in the distal colon or rectum (Pheterogeneity≤0.03). SSB consumption was associated with a statistically significant increase in the incidence of proximal colon cancer (HR per 1-serving/d increment: 1.18; 95% CI: 1.03, 1.34; Ptrend=0.02) and a more pronounced elevation in the mortality of proximal colon cancer (HR: 1.39; 95% CI: 1.13, 1.72; Ptrend=0.002). Similarly, total fructose intake was associated with increased incidence and mortality of proximal colon cancer (HRs per 25-g/d increment: 1.18; 95% CI: 1.03, 1.35; and 1.42; 95% CI: 1.12, 1.79, respectively). Moreover, SSB and total fructose intakes during the most recent 10 y, rather than those from a more distant period, were associated with increased incidence of proximal colon cancer. SSB and total fructose consumption were associated with increased incidence and mortality of proximal colon cancer, particularly during later stages of tumorigenesis.

0593 Maxillomandibular Advancement Referrals and Follow-up After Drug Induced Sleep Endoscopy

Abstract Introduction Several surgical options exist for treating obstructive sleep apnea (OSA), but few correct airway obstruction at multiple levels like maxillomandibular advancement (MMA). MMA has been shown to significantly improve OSA, decrease sleepiness, and also improve quality of life. Despite the accepted success of MMA surgery, it is unclear if patients referred for MMA undergo MMA or are lost to follow-up in real world clinical care. This quality improvement study aims to determine if patients referred for MMA by ENT sleep surgeons then undergo MMA surgery by oral maxillofacial surgeons (OMFS). Methods At our academic urban hospital, all drug induced sleep endoscopy (DISE) cases performed on OSA patients by two otolaryngology sleep surgeons were reviewed over a one year period. Patients who were not recommended for MMA based on DISE findings were excluded. Retrospective chart review included VOTE classification, DISE findings, and referrals for MMA to the OMFS clinic. Other data included age, BMI, past medical history, sleep study data including AHI and oxygen nadir, and if MMA or other OSA treatments were done. Results Out of 408 DISE performed, 58 patients (14.2%) were referred to our OMFS for MMA. Patients’ demographics were: male (48; 82.8%); average age: 51; average BMI: 32.5; 39 (67.2%) with comorbidities. Sleep studies included: 32 HSATs, 22 PSGs, 4 missing. 41 patients (75.9%) had severe OSA. Average O2 nadir was 75%. On DISE, most patients had some level of obstruction at all anatomic subsites (94.8%). All patients had complete obstruction at the level of the palate or velum. 41 (70.7%) also had additional anatomic abnormalities noted including maxillary constriction, midface hypoplasia, retrognathia or micrognathia. From 58 patients recommended for MMA, 35 (60.3%) followed up in OMFS clinic and 11 (31.4%) underwent MMA surgery. Five patients (14.3%) received OATs. 11 patients (19%) had CPAP re-evaluation. 27 patients (46.6%) were lost to follow-up. Conclusion Of patients referred by ENT to OMFS following DISE, only 60% were seen at OMFS clinic and only half of these patients underwent MMA. While some received other treatments, nearly half were lost to follow-up altogether. We propose a revised workflow to improve patient education, acceptance, and coordination of OSA care and follow-up. Support (If Any)

Surgical outcomes of T4b oral cancers: assessment of prognostic factors and a need to re-evaluate the current staging system

T4b oral cancer is a broad umbrella term for all advanced oral cancers, the prognosis of which varies drastically for disease of the same stage, according to the extent of the masticator space involvement. This was a retrospective observational study including all consecutive T4b oral squamous cell carcinoma patients treated surgically between January 2015 and January 2016 and followed up until January 2020. The disease was classified as upper disease or lower disease based on the anatomical location in relation to an imaginary plane passing through the base of the retromolar trigone. The prime objective was to evaluate overall survival and prognostic factors affecting overall survival. The projected 5-year overall and disease-free survival rates were 40.7% and 35.6%, respectively. The assessment of prognostic factors revealed that lower disease (lower anatomical subsites), bone invasion, and lymph nodal spread significantly affected survival. Patients with disease in an upper anatomical location without bone and nodal involvement can achieve fairly good survival (projected 5-year overall survival of 64.2%) when compared to the other subsets of patients. We propose a re-evaluation of the current staging system based on the prognostic features, so that all patients are not considered under a single stage, since their survival differs significantly.

Development and Validation of Machine Learning Models for Predicting Occult Nodal Metastasis in Early-Stage Oral Cavity Squamous Cell Carcinoma

Given that early-stage oral cavity squamous cell carcinoma (OCSCC) has a high propensity for subclinical nodal metastasis, elective neck dissection has become standard practice for many patients with clinically negative nodes. Unfortunately, for most patients without regional metastasis, this risk-averse treatment paradigm results in unnecessary morbidity. To develop and validate predictive models of occult nodal metastasis from clinicopathological variables that were available after surgical extirpation of the primary tumor and to compare predictive performance against depth of invasion (DOI), the currently accepted standard. This diagnostic modeling study collected clinicopathological variables retrospectively from 7 tertiary care academic medical centers across the US. Participants included adult patients with early-stage OCSCC without nodal involvement who underwent primary surgical extirpation with or without upfront elective neck dissection. These patients were initially evaluated between January 1, 2000, and December 31, 2019. Largest tumor dimension, tumor thickness, DOI, margin status, lymphovascular invasion, perineural invasion, muscle invasion, submucosal invasion, dysplasia, histological grade, anatomical subsite, age, sex, smoking history, race and ethnicity, and body mass index (calculated as weight in kilograms divided by height in meters squared). Occult nodal metastasis identified either at the time of elective neck dissection or regional recurrence within 2 years of initial surgery. Of the 634 included patients (mean [SD] age, 61.2 [13.6] years; 344 men [54.3%]), 114 (18.0%) had occult nodal metastasis. Patients with occult nodal metastasis had a higher frequency of lymphovascular invasion (26.3% vs 8.1%; P < .001), perineural invasion (40.4% vs 18.5%; P < .001), and margin involvement by invasive tumor (12.3% vs 6.3%; P = .046) compared with those without pathological lymph node metastasis. In addition, patients with vs those without occult nodal metastasis had a higher frequency of poorly differentiated primary tumor (20.2% vs 6.2%; P < .001) and greater DOI (7.0 vs 5.4 mm; P < .001). A predictive model that was built with XGBoost architecture outperformed the commonly used DOI threshold of 4 mm, achieving an area under the curve of 0.84 (95% CI, 0.80-0.88) vs 0.62 (95% CI, 0.57-0.67) with DOI. This model had a sensitivity of 91.7%, specificity of 72.6%, positive predictive value of 39.3%, and negative predictive value of 97.8%. Results of this study showed that machine learning models that were developed from multi-institutional clinicopathological data have the potential to not only reduce the number of pathologically node-negative neck dissections but also accurately identify patients with early OCSCC who are at highest risk for nodal metastases.

Risk factors for head and neck cancer in more and less developed countries: Analysis from the INHANCE consortium.

We analyzed the pooled case-control data from the International Head and Neck Cancer Epidemiology (INHANCE) consortium to compare cigarette smoking and alcohol consumption risk factors for head and neck cancer between less developed and more developed countries. The location of each study was categorized as either a less developed or more developed country. We compared the risk of overall head and neck cancer and cancer of specific anatomic subsites associated with cigarette smoking and alcohol consumption. Additionally, age and sex distribution between categories was compared. The odds ratios for head and neck cancer sites associated with smoking duration differed between less developed and more developed countries. Smoking greater than 20years conferred a higher risk for oral cavity and laryngeal cancer in more developed countries, whereas the risk was greater for oropharynx and hypopharynx cancer in less developed countries. Alcohol consumed for more than 20years conferred a higher risk for oropharynx, hypopharynx, and larynx cancer in less developed countries. The proportion of cases that were young (<45years) or female differed by country type for some HNC subsites. These findings suggest the degree of industrialization and economic development affects the relationship between smoking and alcohol with head and neck cancer.

Radiation-Induced Esophagitis in Non-Small-Cell Lung Cancer Patients: Voxel-Based Analysis and NTCP Modeling.

The aim of our study is to characterize the risk of radiation-induced esophagitis (RE) in a cohort of Non-Small-Cell Lung Cancer (NSCLC) patients treated with concurrent chemotherapy and photon/proton therapy. For each patient, the RE was graded according to the CTCAE v.3. The esophageal dose-volume histograms (DVHs) were extracted. Voxel-based analyses (VBAs) were performed to assess the spatial patterns of the dose differences between patients with and without RE of grade ≥ 2. Two hierarchical NTCP models were developed by multivariable stepwise logistic regression based on non-dosimetric factors and on the DVH metrics for the whole esophagus and its anatomical subsites identified by the VBA. In the 173 analyzed patients, 76 (44%) developed RE of grade ≥ 2 at a median follow-up time of 31 days. The VBA identified regions of significant association between dose and RE in a region encompassing the thoracic esophagus. We developed two NTCP models, including the RT modality and a dosimetric factor: V55Gy for the model related to the whole esophagus, and the mean dose for the model designed on the thoracic esophagus. The cross-validated performance showed good predictions for both models (ROC-AUC of 0.70 and 0.73, respectively). The only slight improvement provided by the analysis of the thoracic esophageal subsites might be due to the relevant sparing of cervical and lower thoracic esophagus in the analyzed cohort. Further studies on larger cohorts and a more heterogeneous set of dose distributions are needed to validate these preliminary findings and shed further light on the spatial patterns of RE development.

Global burden of oropharyngeal cancer attributable to human papillomavirus by anatomical subsite and geographic region

BackgroundOropharynx is the anatomical site with the highest human papillomavirus (HPV) infection in head and neck. Many studies on HPV prevalence and p16INK4a positivity in oropharyngeal cancer have been published in recent years. We aimed to update the global burden estimates of oropharyngeal cancer attributable to HPV with the latest data and estimate global burden of tonsillar cancer and base of tongue cancer attributable to HPV by region and country. MethodsWe calculated the number of new cancer cases using the Cancer Incidence in Five Continents Volume XI (CI5XI) and country-specific population in 2012 issued by the United Nations. Estimates of HPV prevalence and p16INK4a positivity were obtained from literature search and pooled analyses where necessary. ResultsGlobally the number of oropharyngeal cancer and tonsillar cancer attributable to HPV were 42,000 and 20,000 in 2012, corresponding to AFs of 42.7% and 52.7%. The number of cancer cases attributable to HPV among males was about 4-fold greater than that among females. For both oropharyngeal cancer and tonsillar cancer, AFs were higher in more developed countries. Among HPV positive oropharyngeal cancer cases, 86.7%, 87.8%, and 92.5% could have been prevented by bivalent (2v), quadrivalent (4v), and nonavalent (9v) HPV vaccines. ConclusionsIt is worth considering the inclusion of HPV immunization in males, especially in the regions where oropharyngeal cancer is highly prevalent.