Prognostic factors and risk-stratification model of recurrent or metastatic head and neck squamous cell carcinoma treated with cetuximab containing regimen.

BACKGROUND: In recent years, the addition of cetuximab to chemotherapy has improved treatment outcomes for patients with recurrent/metastatic head and neck squamous cell carcinoma (R/M HNSCC). In this study, we present the real-world survival data of R/M HNSCC patients who received cetuximab-containing regimens from thirteen medical centers in Taiwan, as well as a three-level risk stratification model for this patient population. METHODS: This study enrolled R/M HNSCC patients from thirteen medical centers in Taiwan who received cetuximab-containing regimens from January 1, 2017 to June 6, 2022. The cases were divided into a training cohort and a validation cohort based on the start of treatment. Overall survival (OS) was evaluated in both cohorts and exploratory analysis was performed to identify associated adverse clinical and laboratory factors. The results of the exploratory analysis were used to construct a three-level risk stratification prediction model for OS. RESULTS: A total of 1434 patients with R/M HNSCC were enrolled in this study and received cetuximab-containing regimens. The overall population had a median OS of 8.57 months (95% CI: 8.07 - 9.08). Multivariate analysis of the training cohort identified poor ECOG performance status, heavy alcohol consumption, and prior adjuvant CCRT or lack of prior RT as adverse prognostic factors. Comparison of laboratory data between patients with OS≦6 and OS > 6 also revealed unfavorable factors, including increased white blood cell count, decreased hemoglobin level, increased platelet count, increased absolute neutrophil count, decreased absolute lymphocyte count, and increased neutrophil-to-lymphocyte ratio. Using forward prediction, a three-level risk stratification prediction model was constructed using the variables of ECOG performance status, alcohol consumption, skin metastasis, modality of radiation therapy, hemoglobin level, and neutrophil-to-lymphocyte ratio. The median OS in the low-risk, intermediate-risk, and high-risk groups were 12.02 months (95% CI 10.44-13.61), 7.5 months (95% CI 7.33-8.17), and 4.01 months (95% CI 3.94-4.08), respectively, with a log-rank test p-value < 0.001. CONCLUSION: This study presents a three-level risk stratification model with strong prediction ability for OS in R/M HNSCC patients who received cetuximab-containing regimens. The results are based on real-world data and may provide valuable information for clinicians in treatment planning and future drug development.

Hypoalbuminemia and hypercalcemia are independently associated with poor treatment outcomes of anti-PD-1 immune checkpoint inhibitors in patients with recurrent or metastatic head and neck squamous cell carcinoma.

BACKGROUND: Recent randomized phase III trials have demonstrated the efficacy of anti-programmed cell death 1 (PD-1) immune checkpoint inhibitors (ICIs) in treating patients with recurrent or metastatic head and neck squamous cell carcinoma (RMHNSCC). However, a large proportion of such patients still have poor response. This study aimed to identify biomarkers for predicting anti-PD-1 ICI treatment outcomes . METHODS: We retrospectively analyzed 144 patients with RMHNSCC who received anti-PD-1 ICIs after progression to platinum-based chemotherapy between January 2017 and December 2022 at Kaohsiung Chang Gung Memorial Hospital. Data on clinicopathological parameters, albumin levels, calcium levels, and other pretreatment peripheral blood biomarkers, including total lymphocyte count, neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), lymphocyte-to-monocyte ratio (LMR), and prognostic nutritional index (PNI) were collected and correlated with the treatment outcome of anti-PD-1 ICIs. RESULTS: Low tumor proportion score (TPS), low combined positive score (CPS), NLR ≥ 5, PLR ≥ 300, hypercalcemia, hypoalbuminemia, and PNI < 45 were significantly correlated with poor response of ICIs. The overall response rates were 25% and 3% in patients with calcium < 10 mg/dL and calcium ≥ 10 mg/dL, respectively (P = 0.007). The overall response rates were 6% and 33% in patients with albumin < 4 g/dL and albumin ≥ 4 g/dL, respectively (P < 0.001). Univariate survival analysis showed that low TPS, low CPS, NLR ≥ 5,, hypercalcemia, hypoalbuminemia, and PNI < 45 were significantly associated with worse progression-free survival (PFS) and inferior overall survival (OS). Multivariate analysis revealed that calcium ≥ 10 mg/dL and albumin < 4 g/dL were independent poor prognosticators for worse PFS and inferior OS. The two-year OS rates were 26% and 9% in patients with calcium < 10 mg/dL and ≥ 10 mg/dL, respectively (P < 0.001). The two-year OS rates were 10% and 33% in patients with albumin < 4 g/dL and ≥ 4 g/dL, respectively (P < 0.001). CONCLUSIONS: Hypercalcemia and hypoalbuminemia can potentially predict poor treatment outcomes of anti-PD-1 ICIs in patients with RMHNSCC. Blood calcium and albumin levels may be helpful in individualizing treatment strategies for patients with RMHNSCC.

Mouse models to investigate in situ cell fate decisions induced by p53.

Investigating how transcription factors control complex cellular processes requires tools that enable responses to be visualised at the single-cell level and their cell fate to be followed over time. For example, the tumour suppressor p53 (also called TP53 in humans and TRP53 in mice) can initiate diverse cellular responses by transcriptional activation of its target genes: Puma to induce apoptotic cell death and p21 to induce cell cycle arrest/cell senescence. However, it is not known how these processes are regulated and initiated in different cell types. Also, the context-dependent interaction partners and binding loci of p53 remain largely elusive. To be able to examine these questions, we here developed knock-in mice expressing triple-FLAG-tagged p53 to facilitate p53 pull-down and two p53 response reporter mice, knocking tdTomato and GFP into the Puma/Bbc3 and p21 gene loci, respectively. By crossing these reporter mice into a p53-deficient background, we show that the new reporters reliably inform on p53-dependent and p53-independent initiation of both apoptotic or cell cycle arrest/senescence programs, respectively, in vitro and in vivo.

Targeting DNA junction sites by bis-intercalators induces topological changes with potent antitumor effects.

Targeting inter-duplex junctions in catenated DNA with bidirectional bis-intercalators is a potential strategy for enhancing anticancer effects. In this study, we used d(CGTATACG)2, which forms a tetraplex base-pair junction that resembles the DNA-DNA contact structure, as a model target for two alkyl-linked diaminoacridine bis-intercalators, DA4 and DA5. Cross-linking of the junction site by the bis-intercalators induced substantial structural changes in the DNA, transforming it from a B-form helical end-to-end junction to an over-wounded side-by-side inter-duplex conformation with A-DNA characteristics and curvature. These structural perturbations facilitated the angled intercalation of DA4 and DA5 with propeller geometry into two adjacent duplexes. The addition of a single carbon to the DA5 linker caused a bend that aligned its chromophores with CpG sites, enabling continuous stacking and specific water-mediated interactions at the inter-duplex contacts. Furthermore, we have shown that the different topological changes induced by DA4 and DA5 lead to the inhibition of topoisomerase 2 activities, which may account for their antitumor effects. Thus, this study lays the foundations for bis-intercalators targeting biologically relevant DNA-DNA contact structures for anticancer drug development.

Temporal trends of food consumption patterns in Tuvalu under the context of climate change: COMmunity-based Behavior and Attitude survey in Tuvalu (COMBAT) since 2020.

AIM: The aim of this study was to analyze temporal trends of food consumption patterns, attitudes, and health-related knowledge in Tuvalu, a small Pacific Island country facing the triple threat of obesity, climate change, and food insecurity. METHODS: Two waves of the COMmunity-based Behavior and Attitude (COMBAT) survey were conducted in 2020 and 2022. Descriptive characteristics of changes in obesity proportion, food intake, and sociodemographic factors were assessed. Additionally, this study also integrates individual climate data utilizing satellite-based prediction models, and estimates historical temperature, precipitation, and sea level trends among all islands in Tuvalu. RESULTS: The study revealed a high obesity proportion among adults (69.5% in 2020, 73.2% in 2022) and an increase in the percentage of adolescents with a high waist circumference. Variations in food intake were also observed between the two waves of the survey. CONCLUSIONS: The data collected in the COMBAT study provides valuable insights for future epidemiological research to elucidate the associations and causal relationships between climate change, food security, and non-communicable diseases in Tuvalu.

Clinical outcomes of cetuximab-based treatment for distant metastatic head and neck squamous cell carcinoma: A real-world study using Taiwan Head Neck Society registry database.

BACKGROUND: For R/M HNSCC, the differences in prognosis and treatment options between distant metastasis (DM) and locoregional recurrence, especially in the DM group, remain unclear. METHODS: From the Taiwan Head Neck Society registry database, patients who were diagnosed with R/M HNSCC and received cetuximab-based frontline therapy were collected for analysis. RESULTS: Among the enrolled patients, 59.3% (491/827) belonged to the DM group. The DM group had less primary site of oral cavity, less betel nut chewing, higher lactate dehydrogenase (LDH) levels, and higher LDH/albumin ratio compared with the non-DM group. For the patients with primary site of oral cavity and current smokers, DM coexisted with poorer outcomes. In the DM group, EXTREME-like regimen was more suitable for older patients, those with elevated LDH, and those with higher LDH/albumin ratio than TPExtreme-like regimen. CONCLUSION: DM coexisted with poorer prognosis in certain groups. LDH-associated biomarkers may aid treatment options for DM patients.

Higher Imported Food Patterns Are Associated with Obesity and Severe Obesity in Tuvalu: A Latent Class Analysis.

Background: Tuvalu is a Pacific Island country within the small island developing states that has observed a significant and alarming increase in obesity rates over the past 40 years, affecting ∼60 %-70 % of the current population. Objectives: This study aimed to investigate the association between food patterns and the proportion of obesity in a Pacific Island country. Methods: The 2022 COMmunity-based Behavior and Attitude survey in Tuvalu (COMBAT) included 985 adults with complete data on sociodemographic information and the frequency of consumption of 25 common foods. A latent class analysis determined 4 food patterns. Bayesian multilevel logistic and linear regression models estimated the association between food patterns and the proportion of obesity [body mass index (BMI) ≥30 kg/m2], severe obesity (BMI ≥40 kg/m2), and weight (kg), adjusting for potential confounders and accounting for clustering by region. Results: The latent class analysis revealed 4 food patterns with an entropy of 0.94 and an average posterior probability of class assignment for each individual of 0.97, described as follows: 1) local: locally produced foods with moderate food diversity (proportion of individuals = 28 %); 2) diverse-local: local with greater food diversity (17 %); 3) restricted-imported: more imported with restricted diversity (29 %); and 4) imported: heavily imported with high diversity (26 %). Compared to those following the diverse-local pattern, the odds of having obesity were greater for those classified with the imported pattern [odds ratio (OR): 2.52; 95 % credible interval (CrI): 1.59, 3.99], restricted-imported pattern (OR: 1.89; 95 % CrI: 1.59, 3.99), and local pattern (OR: 1.54; 95 % CrI: 0.94, 2.50). Similar trends were observed for severe obesity while body weight was positively associated with both restricted-imported and imported food patterns. Conclusions: The high consumption of imported foods, together with the low consumption of plant-based foods and protein-rich foods, could be a relevant modifiable lifestyle factor explaining the high levels of obesity and severe obesity in Tuvalu, a Pacific Island country.

Dispatchers trained in persuasive communication techniques improved the effectiveness of dispatcher-assisted cardiopulmonary resuscitation.

BACKGROUND: Early recognition of cardiac arrest and early initiation of bystander cardiopulmonary resuscitation can increase the survival of patients with out-of-hospital cardiac arrest (OHCA). We compared dispatcher-assisted cardiopulmonary resuscitation (DACPR) effectiveness before and after using different communication models in the dispatching center. METHOD: We analyzed dispatch recordings of non-trauma origin OHCA cases received by the Taichung dispatch center between May 1 to September 30, 2021, and November 1, 2021, to March 31, 2022. The dispatchers underwent an 8-hour training intervention consisting of targeted education using a new communication model for DACPR. Several outcome measures were evaluated, including the sustained return of spontaneous circulation and the time to first chest compression. RESULTS: We included 640 cases in the preintervention group and 580 cases in the postintervention group. The return of spontaneous circulation (ROSC) rate, the time to first chest compression, and good neurological outcome were significantly improved in the postintervention group (20.9% vs. 31.0%, p < 0.001;168 seconds vs. 151 seconds, p = 0.004; 2.8% vs. 5.3%, p = 0.024, respectively). In subgroup analyses, the intervention was related to a statistical improvement in ROSC rate among patients whose caller was a family member (18.7% vs. 31.4%, p < 0.001). Among patients whose caller was female, both ROSC and good neurological outcome significantly improved after the intervention (19.8% vs. 36.6%, p < 0.001; 2.7% vs. 7.5%, p = 0.006, respectively). There was a statistical difference between the pre-intervention and post-intervention group with respect to ROSC rate among patients whose caller was family (the adjusted odds ratio:1.78, 95% CI: 0.59-1.25], p < 0.001.) or female (the adjusted odds ratio:3.18,95% CI: 1.77-5.70], p = 0.008.) in the multivariable regression model. CONCLUSION: The new communication model has enhanced the effectiveness of DACPR in terms of the ROSC rate, particularly when the caller was a family member or female, leading to improved rates of ROSC and favorable neurological outcomes.

Cetuximab Treatment beyond Progression in Patients with Recurrent or Metastatic Head and Neck Squamous Cell Carcinoma: A Nationwide Population-Based Study (THNS-2021-08).

BACKGROUND: Little is known regarding the association of cetuximab treatment beyond progression (TBP) with survival among patients with recurrent or metastatic head and neck squamous cell carcinoma (R/M HNSCC). Although immune checkpoint inhibitors (ICIs) are now considered as first-line treatment, not all patients are suitable for ICIs. OBJECTIVE: We conducted a multicenter, retrospective study to evaluate the role of cetuximab TBP in patients with R/M HNSCC after failure of first-line cetuximab-containing chemotherapy. PATIENTS AND METHODS: Patients with R/M HNSCC who had tumor progression after first-line cetuximab-containing chemotherapy were included into our study. Oncologic outcomes were estimated including time to cetuximab treatment discontinuation (TTD), progression-free survival 2 (PFS2), overall survival (OS), overall response rate (ORR), and disease control rate (DCR). Multivariate cox regression analysis with survival were conducted. Subgroup analysis with P16 and programmed death ligand 1 expression were performed. RESULTS: A total of 498 patients were eligible with 259 patients in the TBP group and 239 patients in the non-TBP group. The most common first-line chemotherapy was the EXTREME regimen in both groups. As for second-line treatment, the most common regimen were TPEx in the TBP group and taxane-based chemotherapy in the non-TBP group. Median TTD was 8.7 months in TBP and 5.5 months in non-TBP (p < 0.001). In terms of survival, median OS1 was significant longer in the TBP group than in the non-TBP group [14.1 months versus 10.9 months (p = 0.016)]. Multivariate analysis demonstrated cetuximab TBP was a factor independently associated with OS. CONCLUSIONS: Our retrospective study suggests cetuximab TBP to be effective and to provide better survival for patients with R/M HNSCC after failure of first-line cetuximab-containing chemotherapy. Further prospective studies are warranted to validate the role of cetuximab TBP in R/M HNSCC.

Loss-of-Function but Not Gain-of-Function Properties of Mutant TP53 Are Critical for the Proliferation, Survival, and Metastasis of a Broad Range of Cancer Cells.

Mutations in the tumor suppressor TP53 cause cancer and impart poor chemotherapeutic responses, reportedly through loss-of-function, dominant-negative effects and gain-of-function (GOF) activities. The relative contributions of these attributes is unknown. We found that removal of 12 different TP53 mutants with reported GOFs by CRISPR/Cas9 did not impact proliferation and response to chemotherapeutics of 15 human cancer cell lines and colon cancer-derived organoids in culture. Moreover, removal of mutant TP53/TRP53 did not impair growth or metastasis of human cancers in immune-deficient mice or growth of murine cancers in immune-competent mice. DepMap mining revealed that removal of 158 different TP53 mutants had no impact on the growth of 391 human cancer cell lines. In contrast, CRISPR-mediated restoration of wild-type TP53 extinguished the growth of human cancer cells in vitro. These findings demonstrate that LOF but not GOF effects of mutant TP53/TRP53 are critical to sustain expansion of many tumor types. SIGNIFICANCE: This study provides evidence that removal of mutant TP53, thereby deleting its reported GOF activities, does not impact the survival, proliferation, metastasis, or chemotherapy responses of cancer cells. Thus, approaches that abrogate expression of mutant TP53 or target its reported GOF activities are unlikely to exert therapeutic impact in cancer. See related commentary by Lane, p. 211 . This article is featured in Selected Articles from This Issue, p. 201.

Pediatric neuroimaging findings and clinical presentations of COVID-19: A systematic review.

OBJECTIVES: Symptoms from SARS-CoV-2 infection can involve multiple organ systems. Several reviews discussed the neurologic involvement and neuroimaging findings in adults but research on children is lacking. This study aimed to analyze the incidence of neurologic involvement in patients diagnosed with pediatric inflammatory multisystem syndrome temporally associated with COVID-19 (PIMS-TS) or multisystem inflammatory syndrome in children (MIS-C); and also to summarize current literature on possible neuroimaging findings in SARS-CoV-2 infected children. METHODS: A literature search in six electronic databases was performed to retrieve case series, cohort studies, and cross-sectional studies on neurologic involvement in COVID-19 patients younger than 21 years of age published between December 2019 to September 2023, including COVID-19 patients. RESULTS: A total of 2224 patients with MIS-C from 10 cohorts and cross-sectional studies suggested that neurologic involvement in these subsets ranges from 8.5% to 32.1%. Symptoms included acute encephalitis, seizures, stroke, cranial nerve palsy, nausea/vomiting, and intracranial hypertension. Neuroradiology findings of 114 children from 50 case reports included splenial or acute disseminated encephalomyelitis (ADEM)-like lesions, cytotoxic brain edema, autoimmune demyelinating diseases, ischemic stroke and arteritis, venous thrombosis, intracranial hemorrhage, meningitis, posterior reversible encephalopathy syndrome, anti-N-methyl-D-aspartate receptor autoimmune encephalitis, acute hemorrhagic leukoencephalitis, hydrocephalus, olfactory bulb atrophy, cerebellitis, and acute necrotizing encephalitis. CONCLUSION: Radiologic findings of SARS-CoV-2 infection in the pediatric population are diverse. Neuroimaging studies should be considered in critically ill patients to rule out neurologic involvement and facilitate early interventions.

Genome-wide CRISPR screening identifies a role for ARRDC3 in TRP53-mediated responses.

Whole-genome screens using CRISPR technologies are powerful tools to identify novel tumour suppressors as well as factors that impact responses of malignant cells to anti-cancer agents. Applying this methodology to lymphoma cells, we conducted a genome-wide screen to identify novel inhibitors of tumour expansion that are induced by the tumour suppressor TRP53. We discovered that the absence of Arrestin domain containing 3 (ARRDC3) increases the survival and long-term competitiveness of MYC-driven lymphoma cells when treated with anti-cancer agents that activate TRP53. Deleting Arrdc3 in mice caused perinatal lethality due to various developmental abnormalities, including cardiac defects. Notably, the absence of ARRDC3 markedly accelerated MYC-driven lymphoma development. Thus, ARRDC3 is a new mediator of TRP53-mediated suppression of tumour expansion, and this discovery may open new avenues to harness this process for cancer therapy.

Emergency Medical Services in Taiwan: Past, Present, and Future.

This review assessed the development of Taiwan's emergency medical services (EMS) and focused on the optimizing initiatives of the EMS systems, the current state of Taiwan's EMS system, EMS benchmarks in different regions of Taiwan, EMS response during the coronavirus disease 2019 (COVID-19) pandemic, and future design. In the past decade, there has been a noticeable increase in prehospital services, numerous optimizing initiatives to improve patient prognosis, and the medical oversight model. Taiwan's current EMS system, including the dispatch system, out-of-hospital cardiac arrest (OHCA) patient management, time-sensitive critical illness in prehospital settings, and disaster response, has undergone significant improvements. These improvements have been demonstrated to have a measurable impact on patient outcomes, as supported by medical literature. Each region in Taiwan has developed a unique EMS system with local characteristics, such as the implementation of the Global Resuscitation Alliance 10 steps for OHCA-related quality control, hearing automated external defibrillator program, a five-level prehospital triage system, an island-hopping strategy for patients with major trauma, dispatcher-assisted teamwork for OHCA resuscitation, and optimized prehospital care for acute coronary syndrome patients. In response to the COVID-19 pandemic from 2019 to 2023, Taiwan's EMS implemented measures to combat the outbreak such as interagency collaboration to obtain patient's personal information, to optimize prehospital management initiatives, and to provide financial compensation and personal insurance for emergency medical technicians. The areas that need focus include integrating prehospital and in-hospital information to build a national-level database (One-Stop Emergency Management), increasing public awareness of first responders and emergency casualty care, and evolving the EMS system by incorporating private EMS system, initiating school-based education of paramedicine, and legally recognizing paramedics as medical and health care personnel. By improving these areas, we can better prepare for the future and ensure that Taiwan's EMS system continues to provide high-quality care to those in need.

Exploring the link between home garden use and severe obesity: Insights from a nationwide survey in Tuvalu.

Background: Obesity is prevalent and increasing but understudied across Pacific Islanders. Tuvalu is a South Pacific country with a high obesity rate and faces multiple threats of food insecurity. Home garden serves as a sustainable food source and can be a possible intervention for the obesity pandemic in Tuvalu. This study investigated Tuvaluans' home garden use and obesity, and explored factors associated with increased use of home gardens. Methods: We conducted a nationwide, cross-sectional study in Tuvalu during 2022. Structured questionnaires were administered during the in-person interviews, and trained interviewers measured the height and weight of each participant. The association between home garden use, obesity and severe obesity were tested with univariate and multivariable logistic regression. We also applied overlapping weights to balance the distribution of baseline demographic factors. Results: The average body mass index was 34.87 kilogrammes (kg) / square metre (m2) among the study population of 1024 adults (630 from Funafuti and 394 from other islands in Tuvalu). Overall, people having home gardens was associated lower odds for severe obesity compared to those without a home garden in overlap weighting models (odds ratio (OR) = 0.946, 95% CI = 0.897-0.997, P = 0.039) and the association was stronger in Funafuti (OR = 0.927, 95% CI = 0.866-0.991, P = 0.027) than in the outlying islands (OR = 0.967, 95% CI = 0.889-1.052, P = 0.435). Furthermore, increased age was positively associated with having a home garden in Funafuti, and smoking showed an inverse association. Conclusions: Having a home garden is associated with lower odds of severe obesity in Tuvalu, and the association is stronger in Funafuti. Smokers are less likely to have home gardens, and increased age is positively associated with having home gardens. These findings promote more home garden utilisation and provide evidence for targeted interventions in Tuvalu.

Prognostic utility of neutrophil-to-albumin ratio in surgically treated oral squamous cell carcinoma.

BACKGROUND: We aimed to evaluate the prognostic significance of preoperative neutrophil-to-albumin ratio (NAR) in oral squamous cell carcinoma (OSCC). METHODS: A total of 622 patients with surgically treated OSCC were enrolled. NAR was defined as the absolute neutrophil count divided by the serum albumin level in peripheral blood before the radical surgery. Cox proportional hazards model were used to discover survival outcome-associated factors. RESULTS: The optimal cut-off of NAR to predict overall survival (OS) was determined to be 0.1. In Cox model, high NAR was identified as an independent negative prognosticator of OS, cancer-specific survival, and recurrence-free survival (adjusted hazard ratio: 1.503, 1.958, and 1.727, respectively; all p < 0.05). The NAR-based nomogram accurately predicted OS (concordance index: 0.750). CONCLUSION: Our study suggests that preoperative NAR is a convenient and effective prognostic marker for OSCC and NAR-based nomogram can be a promising prognostic tool in clinical setting.

Evaluation of Sinonasal Outcome Test (SNOT-22) Domains in the Assessment of the Quality of Life in Patients with Nasopharyngeal Carcinoma.

Background: Few instruments are available for assessing the otorhinologic-related quality of life (QOL) in nasopharyngeal carcinoma (NPC) patients. Therefore, we evaluated whether the 22-item Sinonasal Outcome Test (SNOT-22) could be applied to these patients. Methods: Patients diagnosed with NPC, who had been treated with standard protocol and followed up in our institute between 2019 and 2022, were invited to join the cross-sectional study during their clinic visits. All participants completed the SNOT-22 and Eustachian Tube Dysfunction Questionnaire-7 once they were recruited. Confirmatory factor analysis (CFA) was performed to decide the most suitable model for the underlying SNOT-22 subdomains, along with various validity and reliability tests. Results: We identified a total of 275 patients, with 84 (30.5%) women and 191 (69.5%) men. The mean age was 54.1 years (standard deviation: 11.2). Among these patients, 171 (62.1%) were in late stages, and 260 (94.5%) received chemoradiotherapy as treatment. The median interval between primary RT treatment and questionnaire completion was 50 months (interquartile range: 29-93). CFA supported a five-factor model for the SNOT-22 for NPC patients, including nasal, ear/facial, sleep, function, and emotion domains. The internal consistency and test-retest reliability of the SNOT-22 domain score were good. In addition, known-group validity was good for the SNOT-22 total score and domain scores according to the disease recurrence status. Conclusion: Psychometric analyses supported the reliability and validity of a five-domain SNOT-22 for assessing otorhinologic-related QOL in NPC patients.

Lymph node ratio as a survival predictor for head and neck squamous cell carcinoma with multiple adverse pathological features.

BACKGROUND: The study investigates the prognostic significance of lymph node ratio (LNR) on patients with head and neck squamous cell carcinoma (HNSCC) with coexistence of multiple adverse pathological features. METHODS: In total, 100 patients with coexistence of perineural invasion, lymphovascular invasion, and extranodal extension of first primary HNSCC treated with radical surgery followed by adjuvant chemoradiotherapy were enrolled. RESULTS: The optimal LNR cut-off value for predicting overall survival (OS) and cancer specific survival (CSS) was 7%. In Cox model, we observed that LNR ≥7% was a statistically significant unfavorable predictor of OS (HR: 2.689; 95% CI: 1.228-5.889; p = 0.013) and CSS (HR: 3.162; 95% CI: 1.234-8.102; p = 0.016). CONCLUSION: For HNSCC patients with coexistence of multiple adverse pathological features, LNR is an independent survival predictor. Novel intensified treatments are needed for the subgroup of patients with a high LNR.

Deletion of the transcriptional regulator TFAP4 accelerates c-MYC-driven lymphomagenesis.

Many lymphoid malignancies arise from deregulated c-MYC expression in cooperation with additional genetic lesions. While many of these cooperative genetic lesions have been discovered and their functions characterised, DNA sequence data of primary patient samples suggest that many more do exist. However, the nature of their contributions to c-MYC driven lymphomagenesis have not yet been investigated. We identified TFAP4 as a potent suppressor of c-MYC driven lymphoma development in a previous genome-wide CRISPR knockout screen in primary cells in vivo [1]. CRISPR deletion of TFAP4 in Eµ-MYC transgenic haematopoietic stem and progenitor cells (HSPCs) and transplantation of these manipulated HSPCs into lethally irradiated animals significantly accelerated c-MYC-driven lymphoma development. Interestingly, TFAP4 deficient Eµ-MYC lymphomas all arose at the pre-B cell stage of B cell development. This observation prompted us to characterise the transcriptional profile of pre-B cells from pre-leukaemic mice transplanted with Eµ-MYC/Cas9 HSPCs that had been transduced with sgRNAs targeting TFAP4. This analysis revealed that TFAP4 deletion reduced expression of several master regulators of B cell differentiation, such as Spi1, SpiB and Pax5, which are direct target genes of both TFAP4 and MYC. We therefore conclude that loss of TFAP4 leads to a block in differentiation during early B cell development, thereby accelerating c-MYC-driven lymphoma development.