Nutritional status associates with immunotherapy clinical outcomes in recurrent or metastatic head and neck squamous cell carcinoma patients.

BACKGROUND: Beyond programmed death-ligand 1 (PD-L1) assessed by the combined positive score (CPS) and tumor mutational burden (TMB), no other biomarkers are approved for immunotherapy interventions. Here, we investigated whether additional clinical and pathological variables may impact on immunotherapy outcomes in recurrent or metastatic (R/M) head and neck squamous cell carcinoma (HNSCC) patients. METHODS: R/M HNSCC patients treated with immunotherapy were reviewed. Analyzed variables at baseline included: clinicopathological, laboratory, and variables reflecting the host nutritional status such as the prognostic nutritional index (PNI) and albumin. The primary endpoint was progression free survival (PFS). The secondary endpoints were overall survival (OS) and objective response rate (ORR). Univariable and multivariable Cox models were fitted and random forest algorithm was used to estimate the importance of each prognostic variable. RESULTS: A total of 100 patients were treated with immunotherapy; 50% with single agent and 50% with experimental immunotherapy combinations. In the multivariable analysis, both ECOG performance status (HR: 1.73; 95%CI 1.07-2.82; p = 0.03) and PNI levels (10-point increments, HR: 0.66; 0.46-0.95; p = 0.03) were significantly associated with PFS. However, the derived neutrophil to lymphocyte ratio (dNLR) and lactate dehydrogenase (LDH) were not significantly associated with PFS (p-values > 0.15). In the OS analysis, albumin and PNI were the only statistically significant factors in the multivariable model (p < 0.001). CONCLUSIONS: In our cohort, PNI and ECOG performance status were most strongly associated with PFS in R/M HNSCC patients treated with immunotherapy. These results suggest that parameters informative of nutritional status should be considered before immunotherapy.

A Multicentric Prospective Study on Maxillofacial Trauma Due to Road Traffic Accidents: The World Oral and Maxillofacial Trauma Project.

ABSTRACT: The purpose of this prospective multicenter study was to analyze the epidemiology, patterns, and management of maxillofacial fractures due to road traffic accidents (RTAs) worldwide.Between Monday September 30, 2019 and Sunday October 4, 2020,1066 patients with RTAs related fractures were admitted to 14 maxillofacial surgery departments. The following data were analyzed: age, gender, mechanism of injury, alcohol or drug abuse at the time of trauma, maxillofacial fracture site, facial injury severity scale (FISS) score, associated injuries, day and month of trauma, time of treatment, type of treatment and length of hospital stay. Data were analyzed using bivaried and multivaried statistical analysis.Eight hundred seventy patients were male, and 196 were female. The most common mechanism of injury was motorcycle accidents (48%). More than half of the patients had fractures of the middle third of the maxillofacial skeleton. In total, 59% of the study sample underwent open reduction internal fixation. The median facial injury severity scale (3 points) and the medial hospital stay (3 days) were significantly lower in patients with seatbelts and helmet (P  < 0.001).This first prospective, multicenter epidemiological study shows that motorcycle accidents are the leading cause of RTAs related fractures, mostly in young males. Particularly in Australia and Europe, the incidence of RTAs was significantly lower. Moreover, this study found that the severity of maxillofacial lesions was significantly higher in patients without safety devices, with consequent longer hospital stay demonstrating the efficacy of road safety policies in preventing maxillofacial injury.

World Oral and Maxillofacial Trauma (WORMAT) project: A multicenter prospective analysis of epidemiology and patterns of maxillofacial trauma around the world.

BACKGROUND/AIM: The World Oral Maxillofacial Trauma (WORMAT) project was performed to analyze the causes and characteristics of maxillofacial fractures managed in 14 maxillofacial surgery divisions over a 1-year period. METHODS: The following data were collected: age, sex, cause and mechanism of maxillofacial fracture, alcohol and/or drug abuse at the time of trauma, fracture site, Facial Injury Severity Scale score (FISS), associated injury, day of trauma, timing and type of treatment, and length of hospitalization. Statistical analyses were performed using SPSS software. RESULTS: Between 30 September 2019 and 4 October 2020, 2,387 patients (1,825 males and 562 females [ratio 3.2:1], 47.6% aged 20-39 years [mean age 37.2 years, median 33.0 years]) were hospitalised. The main cause of maxillofacial fracture was road traffic accidents (RTA), which were statistically associated with male adults as like as assault, sport, and work (p<0,05). Half of the fractures involved the middle third of the face, statistically associated with fall and assault (p<0.05). Trauma in multiple locations was significantly associated with longer hospital stay (p<0.05). The mean length of hospitalization was 3.9 days (95% Confidence Interval 3.7-4.2). CONCLUSIONS: This prospective, multicenter epidemiological study confirmed that young adult males were the ones most commonly affected by maxillofacial fracture. RTAs and assaults are statistically associated with the adult population, while falls are associated with females and older population.

A multicentric, prospective study on oral and maxillofacial trauma in the female population around the world.

BACKGROUND/AIMS: Approximately 20% of patients with maxillofacial trauma are women, but few articles have analysed this. The aim of this multicentric, prospective, epidemiological study was to analyse the characteristics of maxillofacial fractures in the female population managed in 14 maxillofacial surgery departments on five continents over a 1-year period. METHODS: The following data were collected: age (0-18, 19-64, or ≥65 years), cause and mechanism of the maxillofacial fracture, alcohol and/or drug abuse at the time of trauma, fracture site, Facial Injury Severity Scale score, associated injury, day of trauma, timing and type of treatment, and length of hospitalization. RESULTS: Between 30 September 2019 and 4 October 2020, 562 of 2387 patients hospitalized with maxillofacial trauma were females (24%; M: F ratio, 3.2:1) aged between 1 and 96 years (median age, 37 years). Most fractures occurred in patients aged 20-39 years. The main causes were falls (43% [median age, 60.5 years]), which were more common in Australian, European and American units (p < .001). They were followed by road traffic accidents (35% [median age, 29.5 years]). Assaults (15% [median age, 31.5 years]) were statistically associated with alcohol and/or drug abuse (p < .001). Of all patients, 39% underwent open reduction and internal fixation, 36% did not receive surgical treatment, and 25% underwent closed reduction. CONCLUSION: Falls were the main cause of maxillofacial injury in the female population in countries with ageing populations, while road traffic accidents were the main cause in African and some Asian centres, especially in patients ≤65 years. Assaults remain a significant cause of trauma, primarily in patients aged 19-64 years, and they are related to alcohol use.

Characteristics and age-related injury patterns of maxillofacial fractures in children and adolescents: A multicentric and prospective study.

BACKGROUND/AIMS: Paediatric maxillofacial trauma accounts for 15% of all maxillofacial trauma but remains a leading cause of mortality. The aim of this prospective, multicentric epidemiological study was to analyse the characteristics of maxillofacial fractures in paediatric patients managed in 14 maxillofacial surgery departments on five continents over a 1-year period. METHODS: The following data were collected: age (preschool [0-6 years], school age [7-12 years], and adolescent [13-18 years]), cause and mechanism of the maxillofacial fracture, alcohol and/or drug abuse at the time of trauma, fracture site, Facial Injury Severity Scale score, associated injuries, day of the maxillofacial trauma, timing and type of treatment, and length of hospitalization. Statistical analyses were performed using SPSS software. RESULTS: Between 30 September 2019 and 4 October 2020, 322 patients (male:female ratio, 2.3:1) aged 0-18 years (median age, 15 years) were hospitalized with maxillofacial trauma. The most frequent causes of the trauma were road traffic accidents (36%; median age, 15 years), followed by falls (24%; median age, 8 years) and sports (21%; median age, 14 years). Alcohol and/or drug abuse was significantly associated with males (p < .001) and older age (p < .001). Overall, 474 fractures were observed (1.47 per capita). The most affected site was the mandibular condyle in children <13 years old and the nose in adolescents. The proportion of patients who underwent open reduction and internal fixation increased with age (p < .001). CONCLUSION: The main cause of paediatric maxillofacial fractures was road traffic accidents, with the highest rates seen in African and Asian centres, and the frequency of such fractures increased with age. Falls showed an inverse association with age and were the leading cause of trauma in children 0-6 years of age. The choice of treatment varies with age, reflecting anatomical and etiological changes towards patterns more similar to those seen in adulthood.

A multicentric prospective analysis of maxillofacial trauma in the elderly population.

BACKGROUND/AIMS: The growth of the global elderly population will lead to an increase in traumatic injuries in this group, including those affecting the maxillofacial area, with a heavier load on health systems. The aim of this multicentric prospective study was to understand and evaluate the incidences, causes and patterns of oral and maxillofacial injuries in patients aged over 60 years admitted to 14 maxillofacial surgical departments around the world. METHODS: The following data were collected: gender, cause and mechanism of maxillofacial fracture, alcohol and drug abuse at the time of trauma, fracture site, Facial Injury Severity Scale score, associated injury, day of trauma, timing and type of treatment and length of hospitalization. Statistical analyses were performed using non-parametric and association tests, as well as linear regression. RESULTS: Between 30 September 2019 and 4 October 2020, 348 out of 2387 patients (14.6%), 197 men and 151 women (ratio 1.3:1; mean age 72.7 years), were hospitalized. The main causes of the maxillofacial fractures were falls (66.4%), followed by road traffic accidents (21.5%) and assaults (5.2%). Of the 472 maxillofacial fractures, 69.7% were in the middle third of the face, 28% in the lower third and 2.3% in the upper third. Patients with middle third fractures were on average 4.2 years older than patients with lower third fractures (95% CI 1.2-7.2). Statistical analysis showed that women were more involved in fall-related trauma compared with males (p < .001). It was also shown that road traffic accidents cause more fractures in the lower third (p < .001) and in the middle third-lower third complex compared with upper third (p < .001). CONCLUSIONS: Maxillofacial fractures in the elderly were more frequent in European and Australian centres and affected men slightly more than women. Falls were the leading cause of fractures, especially among women. The middle third of the face was most often affected, and conservative treatment was the most common choice for the management of such patients.

Dietary palmitic acid promotes a prometastatic memory via Schwann cells.

Fatty acid uptake and altered metabolism constitute hallmarks of metastasis1,2, yet evidence of the underlying biology, as well as whether all dietary fatty acids are prometastatic, is lacking. Here we show that dietary palmitic acid (PA), but not oleic acid or linoleic acid, promotes metastasis in oral carcinomas and melanoma in mice. Tumours from mice that were fed a short-term palm-oil-rich diet (PA), or tumour cells that were briefly exposed to PA in vitro, remained highly metastatic even after being serially transplanted (without further exposure to high levels of PA). This PA-induced prometastatic memory requires the fatty acid transporter CD36 and is associated with the stable deposition of histone H3 lysine 4 trimethylation by the methyltransferase Set1A (as part of the COMPASS complex (Set1A/COMPASS)). Bulk, single-cell and positional RNA-sequencing analyses indicate that genes with this prometastatic memory predominantly relate to a neural signature that stimulates intratumoural Schwann cells and innervation, two parameters that are strongly correlated with metastasis but are aetiologically poorly understood3,4. Mechanistically, tumour-associated Schwann cells secrete a specialized proregenerative extracellular matrix, the ablation of which inhibits metastasis initiation. Both the PA-induced memory of this proneural signature and its long-term boost in metastasis require the transcription factor EGR2 and the glial-cell-stimulating peptide galanin. In summary, we provide evidence that a dietary metabolite induces stable transcriptional and chromatin changes that lead to a long-term stimulation of metastasis, and that this is related to a proregenerative state of tumour-activated Schwann cells.

Targeting metastasis-initiating cells through the fatty acid receptor CD36.

The fact that the identity of the cells that initiate metastasis in most human cancers is unknown hampers the development of antimetastatic therapies. Here we describe a subpopulation of CD44bright cells in human oral carcinomas that do not overexpress mesenchymal genes, are slow-cycling, express high levels of the fatty acid receptor CD36 and lipid metabolism genes, and are unique in their ability to initiate metastasis. Palmitic acid or a high-fat diet specifically boosts the metastatic potential of CD36+ metastasis-initiating cells in a CD36-dependent manner. The use of neutralizing antibodies to block CD36 causes almost complete inhibition of metastasis in immunodeficient or immunocompetent orthotopic mouse models of human oral cancer, with no side effects. Clinically, the presence of CD36+ metastasis-initiating cells correlates with a poor prognosis for numerous types of carcinomas, and inhibition of CD36 also impairs metastasis, at least in human melanoma- and breast cancer-derived tumours. Together, our results indicate that metastasis-initiating cells particularly rely on dietary lipids to promote metastasis.

Indications, reconstructive techniques, and results for total glossectomy.

BACKGROUND: The best treatment for advanced tongue tumors remains controversial. Total glossectomy with laryngeal preservation is considered a feasible option, despite its morbidity. METHODS: A retrospective analysis of 12 total glossectomies with laryngeal preservation was performed in order to assess the available reconstruction techniques and analyze survival and functional outcomes. RESULTS: One-year overall survival (OS) and disease-free survival (DFS) rates were 58.3% and 33.3%, respectively, both dropping to 25% after 3 years. Permanent gastrostomy was necessary in 10 patients, although videofluoroscopy revealed adequate tolerance to liquids. Speech intelligibility was satisfactory in 50% of the patients and severely impaired in the remaining 50%. CONCLUSION: Laryngeal preservation in the context of advanced tumors of the tongue without supraglottic invasion carried similar oncologic results to total glossectomy with laryngectomy, but offers a better phonatory function. However, it is usually associated with a higher gastrostomy dependency ratio. A scrupulous selection of candidates is mandatory. © 2016 Wiley Periodicals, Inc. Head Neck 38: E2004-E2010, 2016.