Prophylactic Versus Reactive Megestrol Acetate Use for Critical Body Weight Loss in Patients with Pharyngeal and Laryngeal Squamous Cell Carcinoma Undergoing Concurrent Chemoradiotherapy.

This study compared the effects of megestrol acetate (MA) prophylactic (p-MA) versus reactive (r-MA) use for critical body-weight loss (>5% from baseline) during concurrent chemoradiotherapy (CCRT) in patients with advanced pharyngolaryngeal squamous cell carcinoma (PLSCC).Patients receiving CCRT alone in two phase-II trials were included for analyses. Both the p-MA and r-MA cohorts received the same treatment protocol at the same institution, and the critical body-weight loss, survival, and adverse event profiles were compared.The mean (SD) weight loss was 5.1% (4.7%) in the p-MA cohort (n = 54) vs. 8.1% (4.6%) in the r-MA cohort (n = 50) (p = .001). The percentage of subjects with body-weight loss >5% was 42.6% in the p-MA cohort vs. 68.0% in the r-MA cohort (p = .011). Tube feeding was needed in 22.2% of p-MA vs. 62.0% of r-MA patients (p < .001). Less neutropenia (26.0% vs. 70.0% [p < .001]) and a shorter duration of grade 3-4 mucositis (2.4 ± 1.4 vs. 3.6 ± 2.0 wk [p = .009]) were observed with p-MA treatment. Disease-specific survival, locoregional control, or distant metastasis-free survival did not differ. Less competing mortality from secondary primary cancer resulted in a better overall survival trend in the p-MA cohort.p-MA may reduce body-weight loss and improve adverse event profiles during CCRT for patients with PLSCC.

Cancer-Specific Mortality Odds Ratios in the Food, Accommodation, and Beverage Activities in Italy.

OBJECTIVES: This study investigated cancer-specific mortality risks of workers employed in food, accommodation and beverage (FAB) activities. Methods: We performed a case-control study based on countrywide mortality and National Social Insurance data. Adjusted cancer-specific mortality odds ratios (MOR) were calculated. We modeled occupational exposure as "ever/never been employed" in FAB activities, using other sectors as reference. Analysis was performed by gender, length of employment and year of smoke banning. Results: About 20,000 cancer deaths in FAB were analyzed. Working in restaurants was positively associated with cancer of lung (MOR = 1.24), bladder (MOR = 1.24), pharynx, and larynx. Accommodation was associated with cancer of pharynx (MOR = 1.46), while beverage with cancer of liver (MOR = 1.22). Gender, length of employment and smoke banning were found effective in modifying some risks. Conclusions: Workers in FAB sectors were at risk for several cancers.

Persistent poverty disparities in incidence and outcomes among oral and pharynx cancer patients.

PURPOSE: Disparities in oral cavity and pharyngeal cancer based on race/ethnicity and socioeconomic status have been reported, but the impact of living within areas that are persistently poor at the time of diagnosis and outcome is unknown. This study aimed to investigate whether the incidence, 5-year relative survival, stage at diagnosis, and mortality among patients with oral cavity and pharyngeal cancers varied by persistent poverty. METHODS: Data were drawn from the SEER database (2006-2017) and included individuals diagnosed with oral cavity and pharyngeal cancers. Persistent poverty (at census tract) is defined as areas where ≥ 20% of the population has lived below the poverty level for ~ 30 years. Age-adjusted incidence and 5-year survival rates were calculated. Multivariable logistic regression was used to estimate the association between persistent poverty and advanced stage cancer. Cumulative incidence and multivariable subdistribution hazard models were used to evaluate mortality risk. In addition, results were stratified by cancer primary site, sex, race/ethnicity, and rurality. RESULTS: Of the 90,631 patients included in the analysis (61.7% < 65 years old, 71.6% males), 8.8% lived in persistent poverty. Compared to non-persistent poverty, patients in persistent poverty had higher incidence and lower 5-year survival rates. Throughout 10 years, the cumulative incidence of cancer death was greater in patients from persistent poverty and were more likely to present with advanced-stage cancer and higher mortality risk. In the stratified analysis by primary site, patients in persistent poverty with oropharyngeal, oral cavity, and nasopharyngeal cancers had an increased risk of mortality compared to the patients in non-persistent poverty. CONCLUSION: This study found an association between oral cavity and pharyngeal cancer outcomes among patients in persistent poverty indicating a multidimensional strategy to improve survival.

Alcohol consumption and 10-year mortality in oral and pharyngeal cancer.

BACKGROUND: Previous studies on the association of alcohol drinking with the prognosis of patients with oral and pharyngeal cancer are scarce and conflicting. Most previous studies are surveys from Europe, and examined up to 5 years of overall survival. We therefore evaluated the association between alcohol consumption and 10-year mortality among oral and pharyngeal cancer patients in Japan. METHODS: 2626 eligible cancer patients diagnosed between 1975 and 2010, identified through a hospital-based cancer registry in Japan, were followed up for up to 10 years. Alcohol consumption was used to divide subjects into five categories: non-drinker, ex-drinker, light (≤23 g/day of ethanol), moderate (23 < and ≤ 46 g/day of ethanol), and heavy drinker (> 46 g/day of ethanol), respectively. A Cox proportional hazards regression model was conducted to evaluate the association of alcohol consumption with 10-year all-cause mortality adjusting for sex, age, primary site, cancer stage, number of multiple cancers, surgery, radiotherapy, chemotherapy, smoking status and diagnosis year. RESULTS: Ex-drinker and heavy drinker cases had a significantly higher risk of death than non-drinkers (ex-drinker; HR=1.59; 95% CI,1.28-1.96, heavy drinker; HR=1.36; 95% CI,1.14-1.62). Heavy drinkers had a significantly higher risk of death than non-drinkers in both men and women (men; HR=1.35; 95% CI,1.10-1.65, women; HR=2.52; 95% CI,1.41-4.49). CONCLUSIONS: Among oral and pharyngeal cancer patients, an elevated risk of death was observed for heavy drinkers who consumed more than 46 g/day of ethanol compared with non-drinkers. In addition, this relationship was observed in both men and women.

Safety and outcome of three-dimensional transoral videolaryngoscopic surgery.

BACKGROUND: Transoral videolaryngoscopic surgery (TOVS) is widely used in Japan, and conventional two-dimensional (2D) endoscopic methods have been established. Three-dimensional (3D) endoscopic surgery offers superior distance perception because it provides stereoscopic views. Recently, we have developed 3D endoscopy for TOVS (3D TOVS). METHODS: This study included 46 patients with pharyngeal cancer who underwent 3D TOVS. The perioperative complications and survival curves were retrospectively analyzed. RESULTS: One patient with oropharyngeal cancer who underwent neck dissection and transoral resection simultaneously experienced postoperative hemorrhage of the neck. Another patient with oropharyngeal cancer underwent hemostasis for postoperative pharyngeal hemorrhage. There was one case of aspiration pneumonia. One patient developed cervical lymph node recurrence; however, there was no local recurrence or primary mortality. The 2-year overall survival, disease-specific survival, local control rates, locoregional control rate, and invasive disease-free survival were 90.9%, 100%, 100%, 97.4%, and 79.9%, respectively. CONCLUSIONS: Three-dimensional endoscopy can be safely applied to TOVS.

Quality of life score as a prognosticator for pharyngeal cancer patients treated with radiotherapy.

The purpose of this study was to evaluate the prognostic value of quality of life (QOL) scores acquired not only pre-treatment, but also 1 month after treatment for locoregional control (LRC), distant metastasis-free survival (DMFS), and overall survival (OS) in patients with pharyngeal cancer treated using radiotherapy. Data for 102 patients with naso-, oro-, or hypo-pharyngeal cancer treated between December 2008 and September 2017 were retrospectively analyzed. About 90% of the patients were male. The European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (QLQ-C30) was used for QOL assessments. Associations between QLQ-C30 scores before and 1 month after treatment and outcomes including LRC, DMFS, and OS were analyzed using Cox proportional hazard models. Median follow-up was 37 months (range, 5-117 months). Three-year LRC, DMFS, and OS rates were 77.8%, 60.0%, and 66.5%, respectively. Pre-treatment emotional functioning and diarrhea at 1 month after treatment were identified as significant predictors of LRC. Pre-treatment global QOL and diarrhea at 1 month after treatment were detected as significant predictors of DMFS. Pre-treatment emotional functioning, pre-treatment appetite loss, and diarrhea at 1 month after treatment were detected as significant predictors of OS. Diarrhea at 1 month after treatment was the most powerful QOL variable for predicting LRC, DMFS and OS. Our study revealed that several QOL scores not only before treatment but also 1 month after treatment correlated with LRC, DMFS and OS. In particular, the diarrhea domain of QOL at 1 month after treatment offered the most powerful prognosticator for pharyngeal cancer patients treated with radiotherapy.

Estimating LOCP cancer mortality rates in small domains in Spain using its relationship with lung cancer.

The distribution of lip, oral cavity, and pharynx (LOCP) cancer mortality rates in small domains (defined as the combination of province, age group, and gender) remains unknown in Spain. As many of the LOCP risk factors are preventable, specific prevention programmes could be implemented but this requires a clear specification of the target population. This paper provides an in-depth description of LOCP mortality rates by province, age group and gender, giving a complete overview of the disease. This study also presents a methodological challenge. As the number of LOCP cancer cases in small domains (province, age groups and gender) is scarce, univariate spatial models do not provide reliable results or are even impossible to fit. In view of the close link between LOCP and lung cancer, we consider analyzing them jointly by using shared component models. These models allow information-borrowing among diseases, ultimately providing the analysis of cancer sites with few cases at a very disaggregated level. Results show that males have higher mortality rates than females and these rates increase with age. Regions located in the north of Spain show the highest LOCP cancer mortality rates.

Prognostic significance of hypoxia-inducible factor-1α expression in advanced pharyngeal cancer without human papillomavirus infection.

OBJECTIVE: This study aimed to clarify the association between both hypoxia-inducible factor-1α and glucose transporter type-1 expression and survival outcome in advanced pharyngeal cancer without human papillomavirus infection. METHOD: Twenty-five oropharyngeal and 55 hypopharyngeal cancer patients without human papillomavirus infection were enrolled. All patients had stage III-IV lesions and underwent concurrent chemoradiotherapy or surgery. Hypoxia-inducible factor-1α and glucose transporter type-1 expression were investigated in primary lesions by immunohistochemistry. RESULTS: There were 41 and 39 cases with low and high hypoxia-inducible factor-1α expression, and 28 and 52 cases with low and high glucose transporter type-1 expression, respectively. There was no significant correlation between hypoxia-inducible factor-1α and glucose transporter type-1 expression. In univariate analysis, nodal metastasis, clinical stage and high hypoxia-inducible factor-1α expression, but not glucose transporter type-1 expression, predicted significantly worse prognosis. In multivariate analysis, hypoxia-inducible factor-1α overexpression was significantly correlated with poor overall survival, disease-specific survival and recurrence-free survival. CONCLUSION: High hypoxia-inducible factor-1α expression was an independent risk factor for poor prognosis for advanced human papillomavirus-unrelated pharyngeal cancer.

Clinical significance of tumor-stroma ratio in head and neck cancer: a systematic review and meta-analysis.

BACKGROUND: The clinical significance of tumor-stroma ratio (TSR) has been examined in many tumors. Here we systematically reviewed all studies that evaluated TSR in head and neck cancer. METHODS: Four databases (Scopus, Medline, PubMed and Web of Science) were searched using the term tumo(u)r-stroma ratio. The preferred reporting items for systematic reviews and meta-analyses (PRISMA) were followed. RESULTS: TSR was studied in nine studies of different subsites (including cohorts of nasopharyngeal, oral, laryngeal and pharyngeal carcinomas). In all studies, TSR was evaluated using hematoxylin and eosin staining. Classifying tumors based on TSR seems to allow for identification of high-risk cases. In oral cancer, specifically, our meta-analysis showed that TSR is significantly associated with both cancer-related mortality (HR 2.10, 95%CI 1.56-2.84) and disease-free survival (HR 1.84, 95%CI 1.38-2.46). CONCLUSIONS: The assessment of TSR has a promising prognostic value and can be implemented with minimum efforts in routine head and neck pathology.

High endothelial venules are present in pharyngeal and laryngeal carcinomas and they are associated with better prognosis.

BACKGROUND: Tumors lymphocytic infiltration has prognostic and predictive value. However, the mechanisms involved in lymphocyte recruitment remain poorly characterized. High endothelial venules (HEV) are blood vessels specialized in lymphocyte recruitment, recently showing prognostic significance in some types of cancer. Their implications in laryngeal or pharyngeal cancer is largely unknown. AIM OF THE STUDY: To investigate the possible presence of HEVs in head and neck cancer. MATERIAL AND METHODS: Oropharyngeal (n = 61), hypopharyngeal (n = 53) and laryngeal (n = 21) squamous cell carcinomas were immunohistochemically studied with the MECA-79 antibody, which specifically recognizes HEVs. Histological and clinical factors were correlated with HEVs' presence. RESULTS: HEVs were present in 34% of tumors, showing significant correlations with oropharyngeal localization, higher lymphocytic response, lower tumor budding, lower T status, absence of distant metastases and better overall and progression-free survival. CONCLUSION: HEVs represent an important prognostic factor in head and neck cancer.

Co-treatment with endoscopic laryngopharyngeal surgery and endoscopic submucosal dissection.

OBJECTIVE: Endoscopic laryngopharyngeal surgery (ELPS) is an effective and minimally invasive treatment for pharyngeal cancers. However, the disadvantages of ELPS are the interference of instruments in the operative field and the difficulty in approaching certain areas. To overcome these drawbacks, we began to perform combination treatment of ELPS and endoscopic submucosal dissection (ESD). The aim of the present study was to compare the efficacies of treatment with ELPS alone and ELPS combined with ESD. METHODS: A total of 103 lesions in 73 patients who underwent pharyngeal ELPS for superficial pharyngeal cancer between August 2014 and January 2020 at our hospital were analyzed. Lesions were divided into the ELPS alone group and ELPS combined with ESD group. Lesion characteristics, technical results, adverse events, and long-term outcomes were analyzed. RESULTS: In the ELPS combined with ESD group, procedure speed was shorter than the ELPS alone group (20.2 ± 10.0 mm2/min vs 13.0 ± 6.6 mm2/min, p < 0.001), and R0 resection rate was higher (67.4% vs 45.6%, p = 0.027). There were no significant differences in tumor size, depth of tumor invasion, and adverse events among the 2 groups. These results remained unchanged after propensity score matching. The overall and cause-specific survival rates at 3 years were 96.7% and 100% for the ELPS combined with ESD group and ELPS alone group, respectively. CONCLUSIONS: Combination treatment of ESD and ELPS enabled more efficient resection than ELPS alone. Cooperative treatment of pharyngeal cancer patients involving gastroenterologists and head and neck surgeons is effective and beneficial, and results in favorable long-term outcomes.

Treatment sequence of cetuximab and immune checkpoint inhibitor in head and neck squamous cell carcinoma differentially affects outcomes.

OBJECTIVES: To examine the impact of treatment sequences of Immune checkpoint inhibitor (ICI) and cetuximab on clinical outcomes in patients with recurrent or metastatic (R/M) head and neck squamous cell carcinoma (HNSCC). MATERIALS AND METHODS: Clinicopathologic data were retrospectively collected on patients with R/M HNSCC who received ICI treatment. Association between treatment sequence and clinical outcomes were assessed. RESULTS: A total of 113 patients with R/M HNSCC were analyzed. Patients who had cetuximab prior to ICI had worse overall (HR, 1.83) and progression-free survival (HR, 1.76) compare to those without prior cetuximab. Among patients who had subsequent therapy after ICI, cetuximab-based therapy was associated with a trend toward higher response rate and longer survival than non-cetuximab regimen. CONCLUSION: Our single institution analysis showed that treatment sequence of cetuximab and ICI in R/M HNSCC may affect clinical outcomes. Cetuximab prior to ICI was associated with worse outcomes while the efficacy of cetuximab may be enhanced after ICI therapy.

Association of autoimmunity with survival in patients with recurrent/metastatic head and neck squamous cell carcinoma treated with nivolumab.

OBJECTIVES: Immune checkpoint inhibitors (ICIs) are associated with immune-related adverse events (irAEs) that occur as a consequence of enhanced immune response due to T-cell activation. The objective of this retrospective study was to investigate the association between irAEs and disease outcome in patients with recurrent/metastatic (R/M) head and neck squamous cell carcinoma (HNSCC). MATERIALS AND METHODS: This study included 89 patients with R/M HNSCC who were treated with nivolumab in our center from October 2015 to January 2020. Overall survival (OS) and post-progression survival (PPS) were calculated from the date of nivolumab initiation or from the date of progression on nivolumab respectively to the date of death or censored at the last date of follow up. RESULTS: Twenty-four patients (27%) developed irAEs, with more common thyroiditis (N = 13, 14.6%). ORR did not differ between patients with irAEs (29.2%) and patients without irAEs (21.9%, p = 0.576). Median PFS was similar between the two groups (3.1 months for patients with irAEs vs. 2.6 months for patients without irAEs, p = 0.412). Median OS was significantly longer in patients with irAEs (17.9 vs. 6.3 months in patients without irAEs, log-rank p = 0.004). Additionally, median PPS was significantly improved in patients who developed irAEs (10.2 months vs. 2.8 months for patients without irAEs, log-rank p = 0.001). In multivariate analysis, the development of irAEs and response to nivolumab were shown to be independent prognostic factors for favorable OS and PPS. CONCLUSIONS: The development of irAEs is a strong predictor of improved survival in patients with advanced HNSCC treated with nivolumab.

HPV E2, E4, E5 drive alternative carcinogenic pathways in HPV positive cancers.

The dominant paradigm for HPV carcinogenesis includes integration into the host genome followed by expression of E6 and E7 (E6/E7). We explored an alternative carcinogenic pathway characterized by episomal E2, E4, and E5 (E2/E4/E5) expression. Half of HPV positive cervical and pharyngeal cancers comprised a subtype with increase in expression of E2/E4/E5, as well as association with lack of integration into the host genome. Models of the E2/E4/E5 carcinogenesis show p53 dependent enhanced proliferation in vitro, as well as increased susceptibility to induction of cancer in vivo. Whole genomic expression analysis of the E2/E4/E5 pharyngeal cancer subtype is defined by activation of the fibroblast growth factor receptor (FGFR) pathway and this subtype is susceptible to combination FGFR and mTOR inhibition, with implications for targeted therapy.

Endoscopic laryngopharyngeal surgery for hypopharyngeal lesions.

OBJECTIVES: Transoral approaches for laryngeal/pharyngeal malignancies have been widely accepted as minimally invasive treatment options; however, hypopharyngeal lesions treated by transoral surgery have rarely been reported due to the difficulties in visualizing the hypopharynx. Since 2010, we have treated superficial hypopharyngeal lesions with endoscopic laryngopharyngeal surgery (ELPS), and herein report the outcomes of this transoral procedure. MATERIALS AND METHODS: One hundred and eighteen patients with superficial hypopharyngeal lesions were treated by ELPS from February 2010 to February 2017, and the clinical courses of the patients were reviewed. RESULTS: Four females and 114 males (average: 65.6 y-o) were included in this study. Some patients had multiple lesions and a total of 154 superficial hypopharyngeal lesions (dysplasia: 29, Tis: 52, T1: 44, T2: 20, T3: 9) were treated with ELPS. Ten patients had only dysplasia and no carcinoma. Five patients presented with nodal metastases and 11 patients had simultaneous oropharyngeal lesions. In all cases, the hypopharynx was well visualized with sufficient working space, and no cases required a change in surgical approach. All post-operative complications were safely managed. In regard to the oncological outcomes, of the 108 patients with malignant lesions, the 3-year and 5-year overall survival (OS) rate was 93.6% and 85.5%, respectively. CONCLUSIONS: During ELPS, the hypopharynx was well visualized providing sufficient working space for the resection. The procedure was safe and feasible for superficial hypopharyngeal lesions and exhibited very good oncological outcomes. ELPS is thought to be a very effective surgical alternative for superficial hypopharyngeal lesions.

Tumor radiomic features complement clinico-radiological factors in predicting long-term local control and laryngectomy free survival in locally advanced laryngo-pharyngeal cancers.

OBJECTIVE: To study if pre-treatment CT texture features in locally advanced squamous cell carcinoma of laryngo-pharynx can predict long-term local control and laryngectomy free survival (LFS). METHODS: Image texture features of 60 patients treated with chemoradiation (CTRT) within an ethically approved study were studied on contrast-enhanced images using a texture analysis research software (TexRad, UK). A filtration-histogram technique was used where the filtration step extracted and enhanced features of different sizes and intensity variations corresponding to a particular spatial scale filter (SSF): SSF = 0 (without filtration), SSF = 2 mm (fine texture), SSF = 3-5 mm (medium texture) and SSF = 6 mm (coarse texture). Quantification by statistical and histogram technique comprised mean intensity, standard-deviation, entropy, mean positive pixels, skewness and kurtosis. The ability of texture analysis to predict LFS or local control was determined using Kaplan-Meier analysis and multivariate cox model. RESULTS: Median follow-up of patients was 24 months (95% CI:20-28). 39 (65%) patients were locally controlled at last follow-up. 10 (16%) had undergone salvage laryngectomy after CTRT. For both local control & LFS, threshold optimal cut-off values of texture features were analyzed. Medium filtered-texture feature that were associated with poorer laryngectomy free survival were entropy ≥4.54, (p = 0.006), kurtosis ≥4.18; p = 0.019, skewness ≤-0.59, p = 0.001, and standard deviation ≥43.18; p = 0.009). Inferior local control was associated with medium filtered features entropy ≥4.54; p 0.01 and skewness ≤ - 0.12; p = 0.02. Using fine filters, entropy ≥4.29 and kurtosis ≥-0.27 were also associated with inferior local control (p = 0.01 for both parameters). Multivariate analysis showed medium filter entropy as an independent predictor for LFS and local control (p < 0.001 & p = 0.001). CONCLUSION: Medium texture entropy is a predictor for inferior local control and laryngectomy free survival in locally advanced laryngo-pharyngeal cancer and this can complement clinico-radiological factors in predicting prognosticating these tumors. ADVANCES IN KNOWLEDGE: Texture features play an important role as a surrogate imaging biomarker for predicting local control and laryngectomy free survival in locally advanced laryngo-pharyngeal tumors treated with definitive chemoradiation.

A spatial study of oral & pharynx cancer mortality and incidence in the U.S.A.: 2000-2015.

This is a national scale study of spatial oral and pharynx cancer mortality and incidence clusters in the contiguous U.S.A. Spatial and space-time analyses of incidence and mortality rates of oral and pharynx cancers in the contiguous U.S.A. were done at the county resolution, using mortality data for the years 2000-2014 and incidence data for 2001-2015. The disease surveillance software SaTScan™ is used to identify significant cancer clusters that are non-random. In addition to a cluster analysis, regression analysis was used to adjust cancer incidence and mortality for several covariates or risk factors. This is the first study of the contiguous U.S.A. for oral and pharynx cancer in which mortality and incidence rates are studied together. The geographic clustering for mortality is somewhat different from the clustering for incidence. There exist several significant clusters in the contiguous U.S.A., both for oral and pharynx cancer incidence and for mortality. Some of the significant clusters persisted even after adjusting for several key risk factors. These clusters areas suggest a need for further investigation to identify some local concerns or needs to further address such cancer types in those specific sites. We identified statistically significant spatial and space-time clusters of oral and pharynx cancer for mortality and also for incidence in the contiguous US at the county resolution. The most important risk factors for oral cancer incidence are diabetes, alcohol drinking, and obesity, while the top risk factors for mortality are race, cervical cancer, diabetes, and alcohol drinking.

Global trends in oral and pharyngeal cancer incidence and mortality.

To provide an up-to-date overview of recent trends in mortality from oral and pharyngeal cancer, we analyzed death certification data for 61 countries worldwide provided by the World Health Organization in 2010-2015, and, for selected most populous countries, over the period 1970-2016. For 12 largest countries, we analyzed incidence derived from Cancer Incidence in Five Continents in 1960-2012 for all oral and pharyngeal cancers and by subsites. In 2015, male age-standardized (world population) death rates per 100,000 were 5.03 in the European Union (EU), 8.33 in the Russian Federation, 2.53 in the United States (USA), and 3.04 in Japan; corresponding rates in women were 1.23, 1.23, 0.82, and 0.76. Male mortality decreased over the last decades in several European countries, with earlier and sharper declines in southern Europe; conversely, mortality was still increasing in a few eastern European countries and the United Kingdom. Mortality in men also decreased in Argentina, Australia, and Hong Kong, while it leveled off over more recent calendar years in Brazil, Japan, Mexico, the Republic of Korea, as well as in Australia and the USA. Female mortality slightly rose in various European countries. Overall incidence trends in the largest countries were broadly consistent with mortality ones, but oropharyngeal cancer incidence rose in many countries. Changes in tobacco and alcohol exposure in men over the last decades likely explain the favorable trends in oral and pharyngeal cancer mortality and incidence observed in selected countries worldwide, while increased human papillomavirus infection is likely responsible for the rise in oropharyngeal cancer incidence.

Prognostic role of primary tumor, nodal neck, and retropharyngeal GTVs for unresectable sinonasal cancers treated with IMRT and chemotherapy.

BACKGROUND: We evaluated the prognostic role of gross tumor volumes (GTVs) of primary tumor and positive lymph nodes on overall survival (OS) and progression-free survival (PFS) in locally advanced unresectable sinonasal cancer (SNC) treated with definitive intensity-modulated radiotherapy (IMRT) with or without chemotherapy. METHODS: Primary tumor GTV (GTV-T), pathologic neck nodes GTV (GTV-N), and positive retropharyngeal nodes GTV (GTV-RPN) of 34 patients with epithelial nonglandular SNC receiving IMRT with or without chemotherapy were retrospectively measured. The GTV variables were analyzed in relation with OS and PFS. Survival curves were estimated using the Kaplan-Meier method and compared with the log-rank test. We also estimated the crude cumulative incidence of locoregional relapses only. The optimal volume cutoff value was determined using an outcome-oriented method among the observed values. RESULTS: GTV-T was significantly associated with decreased OS (P=0.003) and PFS (P=0.003). Moreover, patients with disease total volumes (GTV) smaller than 149.44 cm³ had better OS and PFS than patients with higher volumes (P<0.0001 for both). Neck nodal metastasis impacted on OS and PFS (P=0.030 and P=0.033, respectively), but GTV-N did not (P=0.961; P=0.958). Retropharyngeal nodes metastasis was not associated with prognosis (OS: P=0.400; PFS: P=0.104). When GTV-RPN was added to GTV-N (GTV-TN), a relation with PFS (P=0.041) and a trend toward significance for OS (P=0.075) were found. CONCLUSIONS: Our results show that tumor volume is a powerful predictor of outcome in SNC. This could be useful to identify patients with worse prognosis deserving different treatment strategies.

The endoscopic endonasal approach for sinonasal and nasopharyngeal adenoid cystic carcinoma.

OBJECTIVE: To determine factors affecting outcomes for patients with sinonasal and nasopharyngeal adenoid cystic carcinoma (SNACC) treated using the endoscopic endonasal approach (EEA) with preservation of key structures followed by adjuvant radiotherapy (RT). METHOD: Retrospective case series of 30 patients treated at the University of Pittsburgh between 2000 and 2014. Hospital records were reviewed for clinical and pathologic data. Outcome measures included overall survival (OS), disease-free survival (DFS), local recurrence-free survival (LRFS) and distant metastasis-free survival (DMFS) rates. RESULTS: The majority of patients had T4a and T4b disease (23.3%, and 63.3%). Microscopically positive margins were present in 21 patients (63.6%). Positive margins were present in nine patients (30.0%). The mean and median follow-up were 3.97 and 3.29 years. Five-year OS, DFS, LRFS, and DMFS were 62.66%, 58.45%, 87.54%, and 65.26%. High-/intermediate-grade tumors had worse DFS (P = .023), and LRFS (P = .026) (HR = 4.837, 95% CI, 1.181-19.812). No factors were associated with significantly worse DMFS. No patient suffered CSF leak, optic nerve, or internal carotid injury. The mean and median length of hospital stay was 4.1 days and 2.0 days (range: 0-32 days). CONCLUSION: Organ-preserving EEA with adjuvant RT for low-grade SNACC offers 5-year survival similar to that reported by other studies, which include radical, open skull base surgery. Patients with high-grade disease do poorly and may benefit from novel treatment strategies. For low-grade disease, organ-preserving EEA with RT may be the best option, offering a balance of survival, quality of life, and decreased morbidity for patients with this difficult-to-cure disease. LEVEL OF EVIDENCE: 4 Laryngoscope, 130:1414-1421, 2020.