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Background A high incidence of severe acute radiation dermatitis (ARD) has been reported for cancer patients treated by proton beam therapy (PBT). This prospective study investigated the prognostic factors and treatment outcomes of ARD among patients with nasopharyngeal carcinoma (NPC) treated with PBT. Methods Fifty-seven patients with newly diagnosed NPC and treated with PBT were enrolled. ARD was recorded weekly based on the criteria of Common Terminology Criteria for Adverse Events version 4.0 in a prospective fashion at treatment visits (1st to 7th weeks) and 1 week (8th week) and 1 month (11th week) after the completion of PBT. Topical corticosteroid was used when grade 1 ARD appeared, and silver sulfadiazine was added if ARD progressed to grade 2 or more. Results The maximum ARD grade was 1, 2, and 3 in 26 (45.6%), 24 (42.1%), and 7 (12.3%) of the patients, respectively. The peak incidence of grade 2 and 3 ARD was observed during the period of the 6th to 8th weeks. Twenty-four (42.1%) patients received topical corticosteroid alone; 33 (57.9%) patients received the combination of topical corticosteroid and silver sulfadiazine. In the 11th week, most grade 2 and 3 ARD had disappeared and 93.0% of the patients had ARD of grade 1 or lower. In the binary logistic regression model, we identified habitual smoking [odds ratio (OR): 5.2, 95% confidence interval (CI): 1.3–18.8, P = 0.012] and N2 to N3 nodal status (OR: 4.9, 95% CI: 1.6–15.4, P = 0.006) as independent predictors of grade 2 and 3 ARD. Conclusion The results show ARD is a major concern for patients with NPC treated with PBT, especially those with habitual smoking or advanced nodal status. Topical corticosteroid and silver sulfadiazine are effective for treating ARD induced by PBT.

Concurrent chemoradiation therapy (CCRT) is the mainstay treatment for patients with nasopharyngeal carcinoma (NPC). Baroreflex impairment can be a late sequela in patients after neck radiotherapy. We hypothesized that cardiovascular autonomic dysfunction is a progressive process that can begin after CCRT and persists for a longer period.Cardiovascular autonomic function was assessed in 29 newly diagnosed patients with NPC using standardized measures including heart rate response to deep breathing (HRDB), Valsalva ratio (VR), baroreflex sensitivity (BRS), and analyses of heart rate variability (HRV), biomarkers of oxidative stress, and inflammation at three different time points (baseline, immediately after CCRT, and 9 years after enrollment). A healthy control group was recruited for the comparison.Although there was an aging effect on autonomic parameters in both groups during the 9 years of follow-up, the between-group comparison showed that there was a significant decrease in HRDB, VR, and HRV at the 9th year of follow-up in the NPC group. Repeated measures ANOVA after controlling for age and sex showed that both HRDB and triangle index of HRV had statistically significant differences between the two groups.Based on our results, cardiovascular autonomic dysfunction after CCRT is a progressive and dynamic process. Cardiovagal impairment occurs in the early phase and persists in decline, while adrenergic dysfunction is significant only after a 9-year follow-up. In contrast to the current opinion, our study showed that both afferent and efferent baroreflex pathways can be involved after CCRT.

This study explored the effect of transdermal buprenorphine on quality of life and six symptoms in cancer patients with pain.Transdermal opioids offer advantages over traditional routes of administration. The impact of transdermal buprenorphine on quality of life for patients with cancer in Asian populations is unknown.This study employed a single-arm observational repeated measures design. Cancer patients with pain were evaluated prior to treatment (baseline). Over a 4-week treatment period, quality of life and symptoms were assessed at 2 and 4 weeks. This study adhered to the recommendations of STROBE guidelines.This multi-site study was conducted in six hospitals located across northern, middle and southern Taiwan. Adult cancer patients whose pain was previously stable with opioid analgesics and, based on clinical judgement, were able to convert to transdermal buprenorphine treatment were invited to participate. Quality of life was measured with the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire Core 30 (QLQ-C30).Generalised estimating equations showed participants who completed at least one follow-up measurement (N = 80) over 4-weeks had a significant improvement in overall quality of life. Functional status only improved for social functioning. However, symptom severity decreased significantly for nausea/vomiting, pain, insomnia and constipation.The study provides initial evidence supporting transdermal buprenorphine for providing beneficial effects of improving quality of life and reducing severity of symptoms in Asian patients with cancer.The findings of this study can inform the clinical practice that the use of transdermal buprenorphine in cancer patients with pain may also reduce the severity of other symptoms and improve overall quality of life.This study was registered in ClinicalTrials.gov. Identifier: NCT04315831.

Background. In the emergency department (ED), early identification of patients at risk of cardiac arrest is paramount, especially in the context of overcrowding. The shock index (SI) is defined as the ratio of heart rate to systolic blood pressure. It is a tool used for predicting the prognosis of critically ill and injured patients. In this study, we have discussed the relationship between SI and cardiac arrest in the ED. Methods. Patients who experienced cardiac arrest in the ED were classified into two groups, SI ≥ 0.9 and

Background/aim This study investigated whether genetic variations in cyclin D1 (CCND1) are associated with susceptibility to childhood acute lymphoblastic leukemia (ALL). Materials and methods A total of 266 childhood ALL cases and 266 healthy controls were genotyped for CCND1 rs9344 and rs678653. Results There was a significant difference in the genotypic distribution of rs9344 between childhood ALL patients and healthy controls (p=0.0077). Compared to the AA genotype, AG and GG genotypes were associated with significantly decreased risks of childhood ALL with odds ratio (OR) of 0.65 [95% confidence interval (CI)=0.44-0.94, p=0.0234] and 0.45 (95%CI=0.26-0.78, p=0.0040), respectively. Supporting this, allelic frequency distributions between childhood ALL patients and controls was significantly different (OR=0.68, 95%CI=0.53-0.88, p=0.0025). There was no significant difference in the genotypic and allelic distributions of rs678653 between cases and controls. Conclusion CCND1 rs9344, but not rs678653, may serve as a predictive marker of susceptibility for childhood ALL.

Patients with head and neck cancer (HNC) are vulnerable to psychiatric comorbidities, particularly anxiety and depression, and also suffer from cancer stigma. This study aimed to comprehensively compare HNC patients’ stigma, depression, and anxiety, and elucidate the underlying relationships among them. This cross-sectional study recruited inpatients with HNC from a medical center. Measurements included a psychiatric diagnostic interview, the Shame and Stigma Scale (SSS), the Hamilton Anxiety Rating Scale (HAM-A), the Hamilton Depression Rating Scale (HAM-D), the Explanatory Model Interview Catalogue (EMIC), and stressors of HNC patients. Structural equation modeling was used to establish models of potential mechanisms. Those patients having stressors of worry about health (t = 5.21, p

Oral squamous cell carcinoma (OSCC) remains one of the most challenging clinical problems in the field due to its high rate of locoregional and distant metastases. However, studies that assess the association between aspirin use and survival in patients with OSCC are limited. Moreover, patients that recruited from those studies might have tumors that arose from different anatomic regions of the head and neck, including the oral cavity, oropharynx, etc. Since tumors within these distinct anatomic regions are unique in the context of epidemiology and tumor progression, we sought to evaluate the association of aspirin use with squamous cell carcinomas located within the oral cavity only. In this 10-year cohort study, we evaluated aspirin use and survival rates in relation to clinical characteristics as well as duration of aspirin use in patients with OSCC. Our findings suggest that OSCC patients with aspirin use for more than 180 days showed improved overall and disease-specific survival rates. Aspirin also improves survival in patients across various stages of OSCC. Cox regression models indicated that aspirin use was associated with a good prognosis. In conclusion, this evidence indicates that aspirin may be potentially used as an adjuvant therapy for OSCC.

Background: Growing patients with nasopharyngeal carcinoma (NPC) were treated with intensity-modulated proton therapy (IMPT). However, a high probability of severe acute radiation dermatitis (ARD) was observed. The objective of the study is to investigate the dosimetric parameters related to ARD for NPC patients treated with IMPT. Methods: Sixty-two patients with newly diagnosed NPC were analyzed. The ARD was recorded based on the criteria of Common Terminology Criteria for Adverse Events version 4.0. Logistic regression model was performed to identify the clinical and dosimetric parameters related to ARD. Receiver operating characteristic (ROC) curve analysis and the area under the curve (AUC) were used to evaluate the performance of the models. Results: The maximum ARD grade was 1, 2, and 3 in 27 (43.5%), 26 (42.0%), and 9 (14.5%) of the patients, respectively. Statistically significant differences (p < 0.01) in average volume to skin 5 mm with the respective doses were observed in the range 54–62 Cobalt Gray Equivalent (CGE) for grade 2 and 3 versus grade 1 ARD. Smoking habit and N2-N3 status were identified as significant predictors to develop grade 2 and 3 ARD in clinical model, and V58CGE to skin 5 mm as an independent predictor in dosimetric model. After adding the variable of V58CGE to the metric incorporating two parameters of smoking habit and N status, the AUC value of the metric increases from 0.78 (0.66–0.90) to 0.82 (0.72–0.93). The most appropriate cut-off value of V58CGE to skin 5 mm as determined by ROC curve was 5.0 cm3, with a predicted probability of 54% to develop grade 2 and 3 ARD. Conclusion: The dosimetric parameter of V58CGE to skin 5 mm < 5.0 cm3 could be used as a constraint in treatment planning for NPC patients treated by IMPT.

Buprenorphine is one of the strongest opioids used for the relief of cancer pain. This study aims to evaluate the real-world clinical experiences of transdermal buprenorphine used in moderate to severe cancer pain in the Asian population.This is an open-labeled, multicenter, 4-week observational study. Stable cancer pain patients who decided to switch the previous opioid to transdermal buprenorphine will be enrolled in this study. The safety and effectiveness were observed and collected. Pain assessment was performed using a numerical rating scale by the investigators and the Brief Pain Inventory Short Form (BPI-SF) by the patient. The safety profiles included concomitant medications and adverse events (AEs).A total of 83 patients were enrolled in this study. The global pain scores in the BPI, as well as the four individual pain parameters (worst, least, average, and right now), showed a continued decrease (p .05) from week 2 to week 4. Significant improvements were observed in normal work activities, relations with other people, sleep, enjoyment of life, and global BPI pain interference score on week 4. Pain assessments conducted by investigators demonstrated significant, continuous improvements during the study periods. In addition, transdermal buprenorphine demonstrated good safety/tolerability with limited drug-related AEs in the Asian population with cancer pain.This study demonstrated that transdermal buprenorphine in the Asian population has good safety profiles and continued improvements in pain relief, sleep, and pain interferences. Transdermal buprenorphine can be an effective and convenient option as a transdermal opioid for patients with moderate to severe cancer pain in Taiwan. (NCT Number: NCT04315831).

5-methyltetrahydrofolate-homocysteine methyltransferase reductase (MTRR) is responsible for folate metabolism, and we aimed to investigate its genetic role in colorectal cancer (CRC) among Taiwanese.A total of 362 cases and 362 controls were recruited and their MTRR rs1801394 (A66G) and rs1532268 (C524T) genotypes were examined. The behavioral factors and clinicalpathological factors were also analyzed.MTRR rs1801394 genotypes were associated with CRC risk (p for trend=0.0087). In detail, G/G genotype was associated with lower risk (p=0.0049, OR=0.39, 95%CI=0.20-0.76). As for allelic frequency analysis, G allele was also associated with decreased CRC risk (p=0.0026, OR=0.68, 95%CI=0.53-0.88). There was no significant association as for MTRR rs1532268. Among non-smokers and non-alcohol drinkers, those with G/G genotype were at 0.38- and 0.46-fold odds of having CRC. There were no significant protective effects among smokers or alcohol drinkers.MTRR rs1801394 GG genotype can be a protective marker for CRC risk in Taiwan.

Background To evaluate the longitudinal changes of quality of life (QoL) and survival in patients with nasopharyngeal carcinoma (NPC) treated by volumetric-modulated arc therapy (VMAT) versus intensity-modulated radiotherapy (IMRT). Methods One hundred and forty non-distant metastatic NPC patients treated by VMAT (n = 66) or IMRT (n = 74) with simultaneously integrated boost between March 2013 and December 2015 at a single institute were analyzed. QoL was prospectively assessed by the EORTC QLQ-C30 and HN35 questionnaires at the four time points: before RT, RT 42.4 Gy (20 fractions), and 3, 12 months after RT. Results The 3-year locoregional relapse-free survival, distant metastasis-free survival, failure-free survival, and overall survival rates were 96.6, 89.4, 86.1%, and 87.4 for the VMAT group, respectively, compared with 91.4, 90.0, 79.8, and 91.3% for the IMRT group (p value > 0.05). The pattern of QoL changes was similar between the VMAT and IMRT group. No statistically or clinically significant difference in all the QoL scales was observed between VMAT and IMRT group at each time point. Compared to before RT, we observed statistically (p Conclusion The study provides the evidence that the tumor control, survival and changes of QoL is compatible for NPC patients treated by VMAT versus IMRT.

A sustainable transportation infrastructure rating system (STIRS) generally encompasses a wide range of indicators for the comprehensive evaluation of the sustainability of transportation projects....

BACKGROUND/AIM Few studies have examined the contribution of matrix metalloproteinases (MMP) to either diagnosis or prognosis of pterygium. The aim of this study was to investigate the contribution of MMP-1 genotypes to pterygium risk. PATIENTS AND METHODS A total of 134 cases and 268 controls were included and their MMP-1 -1607 (rs1799705) genotypes were examined by polymerase chain reaction-restriction fragment length polymorphism. RESULTS The percentages of 2G/2G, 1G/2G, and 1G/1G for rs1799705 genotypes were 48.5, 36.6 and 14.9% among patients and 33.9, 44.8, and 21.3% among controls (p trend=0.0167). The odds ratios (ORs) after adjusting for age and gender for 1G/2G and 1G/1G genotypes at rs1799705 were 0.54 (95%CI=0.33-0.89, p=0.0168) and 0.46 (95%CI=0.27-0.88, p=0.0192), respectively. Consistently, the adjusted OR for those carrying the 1G allele at MMP-1 -1607 was 0.61 (95%CI=0.41-0.78, p=0.0167), compared with the wild-type 2G allele. CONCLUSION The genotypes at rs1799705 play a role in determining personal susceptibility to pterygium.

Purpose Head and neck cancer (HNC) patients suffer from perceived shame and stigma due to the illness diagnosis, as well as disfigurement following surgery. To measure HNC patients' perception of shame and stigma, the Shame and Stigma Scale (SSS) was developed and preliminarily validated. In this study, we aimed to translate, adapt, and validate the SSS in Chinese. Methods This study consisted of a cross-sectional design with consecutive sampling and consisted of two stages: (1) translation of the SSS into Chinese by two bilingual professionals and (2) examination of the Chinese version of the SSS (C-SSS) for internal consistency, inter-rater reliability, test-retest reliability, construct validity, and concurrent validity. In total, 159 inpatients with HNC (mean age: 56.8 years, 95% males) were enrolled at a medical center in Southern Taiwan. Results The Principal Component Analysis of the C-SSS revealed a five-factor structure: 4 of the 5 factors were replicated in the original SSS, including Shame with Appearance, Regret, Social/Speech Concern, and Sense of Stigma; only factor 4, Self-discrimination, was newly identified in the current study. C-SSS showed acceptable internal validity (Cronbach's α =0.85), test-retest reliability, inter-rater reliability, and fair concurrent validity with the Taiwanese Depression Questionnaire (TDQ), Hamilton Depression Rating Scale (HAM-D), Hamilton Anxiety Rating Scale (HAM-A), and Explanatory Model Interview Catalogue (EMIC). Conclusion The findings of this study indicate that C-SSS is a reliable and valid instrument for evaluating HNC patients' perception of shame and stigma in the Taiwanese population.

Radiation-related extracranial vasculopathy is a common late effect after radiation in patients with nasopharyngeal carcinoma (NPC). We proposed the hypothesis that radiation-related extracranial vasculopathy is a progressive process that can begin immediately after radiotherapy and persist for a longer period, and inflammation and oxidative stress may play a pivotal role in this process. Thirty-six newly diagnosed NPC patients were assessed with B-mode ultrasound for the common carotid artery (CCA) intima media thickness (IMT) measurement as well as surrogate markers at three different stages (baseline, immediately after concurrent chemoradiation therapy (CCRT), and 9 years after enrollment). A healthy control group was also recruited for comparison. Surrogate markers including a lipid profile, HbA1c, inflammation, oxidative stress, and platelet activation markers were assessed. The mean CCA IMT in the NPC group were increased immediately after CCRT (p = 0.043). The mean CCA IMT value after a 9-year follow-up also showed a significant increase in NPC and control group, respectively (p < 0.0001 and p < 0.0001, paired t test). The annual increase mean CCA IMT (mm) was 0.053 ± 0.025 and 0.014 ± 0.013 in NPC and control group, respectively (p < 0.0001). The baseline high sensitivity CRP (hs-CRP), thiol, TBARS, and CD63 level were significantly higher in the NPC group (hs-CRP, p = 0.001, thiol, p < 0.0001, TBARS, p = 0.05, and CD63 level, p = 0.04). The thiol and TBARS levels were significantly lower in NPC patients immediately after CCRT (thiol, p < 0.0001, and TBARS, p = 0.043). The CD62P level was significantly higher while the thiol level was significantly lower in the NPC group after a 9-year follow-up (CD62P level, p = 0.007; and thiol level, p = 0.004). Radiation-related extracranial vasculopathy is a progressive process that begins immediately after radiotherapy with significantly increased carotid IMT compared to the control group during the 9-year follow-up. Chronic inflammation and oxidative stress might serve to drive the process and also contribute to increased platelet activation.

Background Oral cancer with pT1-3N1 without extracapsular extension of the lymph node is classified as stage III according to the eighth edition of the AJCC staging system. Outcomes of a subgroup of patients classified as having stage III oral cancer with single nodal metastasis are observed to be various clinically. Therefore, such clinical outcomes for subgroup analyses in this cohort are necessary. Methods Patients with pT1-3N1 (based on the eighth edition of the AJCC staging system) oral cancer who underwent surgery between 2007 and 2016 were enrolled retrospectively for survival analyses. Results A total of 105 patients—including 28 patients with pT1N1 disease and 77 patients with pT2-3N1 disease—participated in the study. Pathological T classification was the only statistically significant prognosticator according to univariate analysis. The patients with pT1N1 disease showed better 5-year overall survival (OS), disease specific survival (DSS), and disease free survival (DFS) than those with pT2-3N1 disease (pT1N1 vs pT2-3N1, OS: 96.4% vs 72.2%, p = 0.004; DSS: 96.4% vs 77.3%, p = 0.021; DFS: 84.6% vs 62.3%, p = 0.023). Besides, there was no potential clinicopathological confounder which is significant associated with different pathological T classifications in this unique cohort. Conclusions Patients in the pT1N1 subgroup have significantly favorable prognosis than those with pT2-3N1 disease. Down-staging and reclassifying pT1N1 subgroup patients with oral cancer may be considered in tumor staging. Graphical Abstract

Simple Summary Even after the implementation of intensity-modulated radiotherapy (IMRT), nasopharyngeal cancer (NPC) survivors may continue to exhibit several physical symptoms that negatively affect long-term quality of life (QoL). An NPC patient cohort study (n = 682) was conducted to examine the potential mediating effect of QoL (evaluated at multiple treatment-related time points) on the cancer stage–mortality association. Patients with advanced NPC exhibited low global health QoL and high QoL-HN35 symptom pre-IMRT, 3 months post-IMRT, and 2 years post-IMRT. Global health QoL and QoL-HN35 symptom scores 2 years after IMRT explained 49.4% and 39.4% of the excessive effect of advanced NPC on mortality risk. Our findings indicate that global health QoL and QoL-HN35 symptom 2 years after IMRT are key mediators of the relationship between advanced NPC and high mortality. These findings emphasize the significance of QoL-HN35 symptom and global health QoL-associated medical support and care for patients with NPC who received IMRT. Abstract Background: Quality of life (QoL) attained before, during, or after treatments is recognized as a vital factor associated with therapeutic benefits in cancer patients. This nasopharyngeal cancer (NPC) patient longitudinal study assessed the relationship among QoL, cancer stage, and long-term mortality in patients with nasopharyngeal carcinoma (NPC) treated with intensity-modulated radiotherapy (IMRT). Patients and Methods: The European Organization for Research and Treatment of Cancer (EORTC) core QoL questionnaire (QLQ-C30) and the head and neck cancer-specific QoL questionnaire module (QLQ-HN35) were employed to evaluate four-dimensional QoL outcomes at five time points: pre- (n = 682), during (around 40 Gy) (n = 675), 3 months (n = 640), 1 year (n = 578) and 2 years post-IMRT (n = 505), respectively, for 682 newly diagnosed NPC patients treated between 2003 and 2017 at a single institute. The median followed-up time was 7.5 years, ranging from 0.3 to 16.1 years. Generalized estimating equations, multivariable proportional hazards models, and Baron and Kenny’s method were used to assess the investigated effects. Results: Advanced AJCC stage (III–IV) patients revealed a 2.26-fold (95% CI—1.56 to 3.27) higher covariate-adjusted mortality risk than early-stage (I–II) patients. Compared with during IMRT, advanced-stage patients had a significantly low global health QoL and a significantly high QoL-HN35 symptom by a large magnitude at pre-, 3 months, and 2 years post-IMRT. QoL scales at pre-IMRT, 1 year, and 2 years post-IMRT were significantly associated with mortality. The effect changes of mortality risk explained by global health QoL, QoL-C30, and QoL-HN35 symptom were 5.8–9.8% at pre-IMRT but at 2 years post-IMRT were 39.4–49.4% by global health QoL and QoL-HN35 symptoms. Conclusions: We concluded advanced cancer stage correlates with a long-term high mortality in NPC patients treated with IMRT and the association is partially intermediated by QoL at pre-IMRT and 2 years post-IMRT. Therefore, QoL-HN35 symptom and global health QoL-dependent medical support and care should be focused and tailored at 2 years post-IMRT.

This study aims to evaluate the relationship between human ribophorin II (RPN2) and the effect of treatment using induction therapy with docetaxel, cisplatin, and fluorouracil (TPF) for p-16 negative locally advanced head and neck squamous cell carcinoma (HNSCC). A total of 203 patients with locally advanced p-16 negative HNSCC who received induction chemotherapy with TPF at the Kaohsiung Chang Gung Memorial Hospital between 2009 and 2014 were enrolled. Immunohistochemistry (IHC) for RPN2 was examined and correlated with treatment outcome. Our study showed that RPN2 overexpression was significantly correlated with a poor response to induction chemotherapy with TPF. Both RPN2 overexpression and clinical N1 to N3 stages represented adverse prognostic factors for progression-free survival (PFS) and overall survival (OS). RPN2 might be a predictive marker for treatment response to induction chemotherapy. Further clinical trials are needed to determine the therapeutic significance of RPN2 in patients with HNSCC.

This study investigated whether genetic variations in cyclin D1 (CCND1) are associated with susceptibility to childhood acute lymphoblastic leukemia (ALL).A total of 266 childhood ALL cases and 266 healthy controls were genotyped for CCND1 rs9344 and rs678653.There was a significant difference in the genotypic distribution of rs9344 between childhood ALL patients and healthy controls (p=0.0077). Compared to the AA genotype, AG and GG genotypes were associated with significantly decreased risks of childhood ALL with odds ratio (OR) of 0.65 [95% confidence interval (CI)=0.44-0.94, p=0.0234] and 0.45 (95%CI=0.26-0.78, p=0.0040), respectively. Supporting this, allelic frequency distributions between childhood ALL patients and controls was significantly different (OR=0.68, 95%CI=0.53-0.88, p=0.0025). There was no significant difference in the genotypic and allelic distributions of rs678653 between cases and controls.CCND1 rs9344, but not rs678653, may serve as a predictive marker of susceptibility for childhood ALL.

e18013 Background: Cetuximab significantly improved survival outcomes of recurrent or metastatic head and neck squamous cell carcinoma (R/M HNSCC) when combined with chemotherapy. The aim of this study was to explore clinical outcomes, prognostic factors, and risk stratification model for R/M HNSCC patients who received cetuximab-containing regimens based on a real-world, multicenter Taiwanese patient cohort. Methods: This is a retrospective study involving 12 oncology institutions in Taiwan. All R/M HNSCC patients who received cetuximab-containing regimens from January 2017 to December 2020 were included in this study. Prognostic factors were evaluated by univariate/ multivariate analysis. The factors that showed significant differences (p < 0.05) were selected to establish the prediction model. The receiver operating characteristic (ROC) curve was obtained to select cut-off values as a reference for continuous variables. The risk score system incorporated both continuous and categorical factors. The score was determined according to hazard ratio. Results: A total of 818 R/M HNSCC patients were included in this study. Patient characteristics were as following: median age, 56 years; performance status (PS) 0/1/≧2, 16.0%/70.4%/13.3%; oral/ oropharynx/ hypopharynx/ larynx/ others, 51.5%/17.5%/19.7%/6.4%/5.0%; stage at initial diagnosis (AJCC8), 0/I/II/III/IVA/IVB/IVC/unknown, 0.2%/5.9%/8.1%/7.1%/ 35.5%/18.0%/6.7%/18.6%; locoregional recurrence/ distant metastasis/ unknown, 38.4%/ 56.0%/ 5.6%; site of distant metastasis, lung/ distant lymph node/ bone/ liver/ skin/ brain, 60.3%/ 37.1%/ 18.8%/ 6.3%/ 8.1%/ 3.3%; cetuximab-PF/ cetuximab-non-PF regimen, 56.6%/ 43.4%. The median overall survival (mOS) was 10.0 months (95% confidence interval [CI] 9.1-10.9 months). Multivariate analysis disclosed poor prognostic factors on OS, including poor PS, smoking history, R2 resection of primary surgery, present distant metastasis at bone, cetuximab combined with non-PF regimen. In addition, HB and neutrophil to lymphocyte ratio (NLR) were shown to have significant difference between treatment responders and non-responders (inc. SD pts). Risk-stratification model was established including factors: PS, smoking history, bone metastasis, hemoglobin level, and NLR. The mOS of the three risk groups stratified from the prediction model were 13.0/7.0/4.0 months (p < 0.001). Conclusions: Poor prognostic factors for R/M HNSCC treated with cetuximab-based regimens includes poor PS, smoking history, R2 resection of primary surgery, bone metastasis, and non-PF regimen. In this study, the risk-stratification model for cetuximab-based treatment was established using some of the identified prognostic factors help to predict the overall survival for R/M HNSCC patients.

Background To investigate the toxicity, changes of quality of life (QOL), and survival for patients with nasopharyngeal cancer (NPC) treated by concurrent chemoradiotherapy (CCRT) with simultaneously integrated boost volumetric-modulated arc therapy (SIB-VMAT). Methods A total of 68 NPC patients treated by CCRT with SIB-VMAT technique were collected. QOL was longitudinally assessed by the EORTC QLQ-C30 and HN35 questionnaires at the 4 time points: baseline, 42.4 Gy (20 fractions), and 3, 12 months after CCRT. Results The 4-year locoregional relapse free, distant metastasis free, failure free, and overall survival rates were 97.0%, 86.4%, 82.0%, and 88.1%, respectively. The 4-year cumulative incidence rate of late toxicities with grade 3 or more was 3.0%. One year after CCRT, most QOL scales, except some oral related symptoms, recovered to baseline level. Conclusion CCRT with SIB-VMAT produces excellent locoregional control, few severe late toxicity, and good general health status for NPC patients.

Patients with advanced head and neck squamous cell carcinoma (HNSCC) usually show a dismal prognosis. It is this worthwhile to develop new, effective therapeutic regimens for these patients, such as molecular targeted therapy, which is promising as an alternative or combination treatment for HNSCC. The mammalian target of rapamycin (mTOR) pathway, which plays an important role in the carcinogenesis of HNSCC, is the most frequently activated, and is thus worthy of further investigation. In this study, two human HNSCC cell lines, FaDu and SAS, were evaluated for cell growth with trypan blue staining and tumor growth using an orthotopic xenograft model. The immunohistochemical expression of mTOR in the subcutaneous xenograft model and the inhibitory effects of docetaxel on the growth and state of activation of the PI3K/mTOR pathway were also evaluated and examined by colony formation and Western blot, respectively. Cell proliferation and migration were measured by water-soluble tetrazolium salt (WST-1) and OrisTM cell migration assay, respectively. Furthermore, the effects of rapamycin and BEZ235, a phosphatidylinositol 3-kinases (PI3K) and mTOR inhibitor in combination with docetaxel or CCL20 were evaluated in the FaDu and SAS cells. The results showed that the expression of mTOR was significantly higher in the SAS and FaDu xenograft models than in the control. Docetaxel treatment significantly suppressed HNSCC cell proliferation and migration in vitro via the PI3K/mTOR/CCL-20 signaling pathway. Additionally, when administered in a dose-dependent fashion, mTOR inhibitors inhibited the growth and migration of the HNSCC cells. This combination was synergistic with docetaxel, resulting in almost complete cell growth and migration arrest. In conclusion, docetaxel significantly inhibited HNSCC cell proliferation and migration in vitro via the PI3K/mTOR/CCL-20 signaling pathway. The synergistic and additive activity of mTOR inhibitors combined with docetaxel shows potential as a new treatment strategy for HNSCC.

Oral squamous cell carcinoma (OSCC) remains one of the most challenging clinical problems in the field due to its high rate of locoregional and distant metastases. However, studies that assess the association between aspirin use and survival in patients with OSCC are limited. Moreover, patients that recruited from those studies might have tumors that arose from different anatomic regions of the head and neck, including the oral cavity, oropharynx, etc. Since tumors within these distinct anatomic regions are unique in the context of epidemiology and tumor progression, we sought to evaluate the association of aspirin use with squamous cell carcinomas located within the oral cavity only. In this 10-year cohort study, we evaluated aspirin use and survival rates in relation to clinical characteristics as well as duration of aspirin use in patients with OSCC. Our findings suggest that OSCC patients with aspirin use for more than 180 days showed improved overall and disease-specific survival rates. Aspirin also improves survival in patients across various stages of OSCC. Cox regression models indicated that aspirin use was associated with a good prognosis. In conclusion, this evidence indicates that aspirin may be potentially used as an adjuvant therapy for OSCC.

Background: To assess the presence of adverse pathological features at the time of salvage total laryngectomy (TL) associated with oncologic outcome. Methods: Ninety patients with persistent/locally recurrent disease and who subsequently underwent salvage TL after definitive treatment by radiation alone (RTO) or concurrent chemo-radiation (CCRT) from 2009 to 2018 were retrospectively enrolled. Kaplan&ndash, Meier methods were used to estimate overall survival (OS), disease-specific survival (DSS), and disease-free survival (DFS). Results: Lymphovascular invasion (LVI), perineural invasion, positive margin, and stage IV disease were associated with worse survival in the univariate analysis. In the multivariate analysis, the presence of LVI and positive margin were both independent negative predictors in OS (LVI: adjusted hazard ratio (aHR) = 2.537, 95% CI: 1.163&ndash, 5.532, p = 0.019, positive margin: aHR = 5.68, 95% CI: 1.996&ndash, 16.166, p = 0.001), DSS (LVI: aHR = 2.975, 95% CI: 1.228&ndash, 7.206, p = 0.016), positive margin: aHR = 11.338, 95% CI: 2.438&ndash, 52.733, p = 0.002), and DFS (LVI: aHR 2.705, 95% CI: 1.257&ndash, 5.821, p = 0.011, positive margin (aHR = 6.632, 95% CI: 2.047&ndash, 21.487, p = 0.002). Conclusions: The presence of LVI and positive margin were both associated with poor OS, DSS, and DFS among patients who underwent salvage TL after failure of RTO/CCRT. The role of adjuvant therapy for high-risk patients after salvage TL to improve the chance of survival requires more investigation in the future.

Hui-Ching Chuang,1,2 Ming-Hsien Tsai,1,2 Yu-Tsai Lin,1,2 Ming-Huei Chou,3,4 Tai-Lin Huang,2,5 Tai-Jan Chiu,2,5 Hui Lu,1 Fu-Min Fang,2,6 Chih-Yen Chien1,2,7 1Department of Otolaryngology, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan; 2Kaohsiung Chang Gung Head and Neck Oncology Group, Cancer Center, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan; 3The Graduate Institute of Clinical Medical Sciences, Chang Gung University College of Medicine, Kaohsiung, Taiwan; 4Center for General Education, Cheng-Shiu University, Kaohsiung, Taiwan; 5Department of Hematology-Oncology, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan; 6Department of Radiation Oncology, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan; 7Institute for Translational Research in Biomedicine, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, TaiwanCorrespondence: Chih-Yen Chien Email cychien3965@adm.cgmh.org.twPurpose: This study aimed to investigate the clinical impacts of the pretreatment peripheral blood ratios of lymphocytes, monocytes and neutrophils among patients with hypopharyngeal cancer/laryngeal cancer.Patients and Methods: A total of 141 people with cases of hypopharyngeal cancer/laryngeal cancer were enrolled to evaluate the clinical impacts of the systemic inflammation response index (SIRI), neutrophil–lymphocyte ratio (NLR) and lymphocyte–monocyte ratio (LMR) in pretreatment blood among patients with laryngeal/hypopharyngeal cancer between January 2012 and December 2014.Results: Those patients with higher pretreatment LMR (> 2.99) showed a significantly higher 5-year complete response rate (CR) (69% vs 31%) than those with lower LMR (≤ 2.99, p = 0.006). Additionally, those patients with lower pretreatment SIRI (< 3.26) showed a significantly higher 5-year CR (90% vs 10%) than those with higher SIRI (≥ 3.26, p < 0.001). Patients with higher LMR had better 5-year overall survival (OS) (p = 0.01) and 5-year progression-free (PFS) (p = 0.005) rates than those with lower LMR in univariate analysis. Patients with lower SIRI had better 5-year OS (p < 0.001) and 5-year PFS (p < 0.001) than those with higher SIRI in univariate analysis. In the Cox regression analysis, SIRI (HR = 1.941, [95% CI: 1.223– 3.081], p = 0.005) and N classification (HR = 2.203, [95% CI: 1.327– 3.657], p = 0.002) were independent variables of 5-year OS. In addition, SIRI (HR= 2.127, [95% CI: 1.214– 3.725], p = 0.008), T classification (HR = 2.18, [95% CI: 1.072– 4.433], p = 0.031), and N classification (HR = 2.329, [95% CI: 1.395– 3.889], p = 0.001) were independent variables of 5-year PFS.Conclusion: Pretreatment SIRI is superior to LMR in predicting treatment response and clinical outcomes among patients with laryngeal/hypopharyngeal cancer treated by CRT/RTO. SIRI may be adopted in the treatment of laryngeal/hypopharyngeal cancer by CRT/RTO.Keywords: head and neck squamous cell carcinoma, hypopharyngeal cancer, laryngeal cancer, systemic inflammation response index, neutrophil–lymphocyte ratio, lymphocyte–monocyte ratio

Background Systemic inflammation and nutritional status both play roles in the survival of cancer patients. Therefore, it is important to understand the effects of prognostic nutritional index (PNI) and lymphocyte-to-monocyte ratio (LMR) on the survival of patients with advanced p16-negative oropharyngeal cancer. Methods A total of 142 patients diagnosed with advanced p16-negative oropharyngeal cancer between 2008 and 2015 were enrolled in this study. All patients received primary treatment with definite concurrent chemoradiotherapy (CCRT). Optimal cutoff values for PNI and LMR were determined using receiver operating characteristic curves for survival prediction. Survival rates for different level of PNI and LMR were estimated and compared using Kaplan–Meier method and log-rank test to see if there were significant effects on these end points, including 5-year overall survival (OS), disease-specific survival (DSS) and disease-free survival (DFS) rates. The effects of PNI and LMR on survival were assessed using Cox regression model adjusted for other prognostic factors. Results The results showed the optimal cutoff values for PNI and LMR were 50.5 and 4.45, respectively. A high PNI (≧50.5) was significantly improved the 5-year OS. A low LMR ( Conclusions Elevated pretreatment PNI and LMR are both favorable prognosticators in advanced p16-negative oropharyngeal cancer patients undergoing CCRT.

ObjectiveTo determine the predictive factors of postoperative hospital stay and total hospital medical cost among patients who underwent total laryngectomy.MethodsA total of 213 patients who underwent total laryngectomy in a tertiary referral center for tumor ablation were enrolled retrospectively between January 2009 and May 2018. Statistical analyses including Pearson's chi-squared test were used to determine whether there was a significant difference between each selected clinical factors and outcomes. The outcomes of interest including postoperative length of hospital stay and inpatient total medical cost. Logistic regression analyses were performed to reveal the relationship between clinical factors and postoperative length of hospital stay or total inpatient medical cost.ResultsPreoperative radiotherapy (p = 0.007), method of wound closure (p < 0.001), postoperative serum albumin level (p = 0.025), and postoperative serum hemoglobin level (p = 0.04) were significantly associated with postoperative hospital stay in univariate analysis. Postoperative hypoalbuminemia (odds ratio [OR]: 2.477; 95% confidence interval [CI]: 1.189-5.163; p = 0.015) and previous radiotherapy history (OR 2.194; 95% CI: 1.228-3.917; p = 0.008) are independent predictors of a longer postoperative hospital stay in multiple regression analysis. With respect to total inpatient medical cost, method of wound closure (p < 0.001), preoperative serum albumin level (p = 0.04), postoperative serum albumin level (p < 0.001), and history of liver cirrhosis (p = 0.037) were significantly associated with total inpatient medical cost in univariate analysis. Postoperative hypoalbuminemia (OR: 6.671; 95% CI: 1.927-23.093; p = 0.003) and microvascular free flap reconstruction (OR: 5.011; 95% CI: 1.657-15.156; p = 0.004) were independent predictors of a higher total inpatient medical cost in multiple regression analysis.ConclusionsPostoperative albumin status is a significant factor in predicting prolonged postoperative hospital stay and higher inpatient medical cost among patients who undergo total laryngectomy. In this cohort, the inpatient medical cost was 48% higher and length of stay after surgery was 35% longer among hypoalbuminemia patients.

Background: Aspirin use has been associated with improved survival rates in various cancers. However, it remains unclear if aspirin confers a survival benefit on patients with nasopharyngeal carcinoma (NPC). The aim of this study was to assess the associations between aspirin use and survival in different stages of NPC. Methods: This is a 10-year retrospective cohort study of NPC patients. A total of 565 NPC patients were recruited after we performed a 1:4 propensity score match between aspirin users and non&ndash, users. Cox regression models with adjusted covariates were employed to evaluate factors that influence the survival rate of NPC patients. Results: The Kaplan-Meier analysis revealed that the overall survival (p &lt, 0.0001) and disease-specific survival (p &lt, 0.0001) rates of 180-day aspirin users increased. Increased survival rates were also observed in 180-day aspirin users with Stages III and IV, T, N1 and 2, and N3 categories. Cox regression models indicated that factors, including aspirin use (univariate: HR = 0.28, 95% CI = 0.14&ndash, 0.55, p &lt, 0.001, multivariate: HR = 0.23, 95% CI = 0.12&ndash, 0.46, p &lt, 0.001), were independent prognostic factors for survival. Conclusions: Aspirin use for more than 180 days is associated with an increased survival rate and is a positive independent prognostic factor in NPC.

Background: To evaluate the impact of gross tumor volume (GTV) on toxicities and quality of life (QoL) for patients with nasopharyngeal carcinoma (NPC) treated by concurrent chemoradiotherapy with simultaneously integrated boost technique (chemo-SIB-IMRT). Methods: A total of 278 NPC patients with stage II-IVb treated by chemo-SIB-IMRT were enrolled. Toxicities were evaluated according to CTCAE version 4.03. QoL outcomes (n=219) were measured by using the EORTC QLQ-C30 and HN35 questionnaires at the time point of 12 months after chemo-SIB-IMRT. Results: A higher GTV was observed to be significantly associated with a higher mean or maximal dose in most organs at risk, together with more severe acute (mucositis, dermatitis, weight loss, and use of analgesic) and late toxicities (xerostomia, neck fibrosis, and radiation neuropathy). A linear regression model revealed that a higher GTV was significantly associated with a decline in role functioning and an increment in taste/smell, speech, social eating, opening mouth, dry mouth, and sticky saliva. Conclusion: GTV is the determining factor of some acute and late toxicities and QoL scales for NPC patients treated by chemo-SIB-IMRT.

Background/Aim: Mounting evidence has shown that miRNAs play a critical role in the regulation of hematopoiesis of cell proliferation and apoptosis as well as in tumorigenesis. The miR146a rs2910164 polymorphism, which is closely responsive for its expression, has been reported to associate with the risk of several solid cancers. The study aimed at examining the association of the it with susceptibility to childhood acute lymphoblastic leukemia (ALL) in Taiwan. Materials and Methods: We recruited 266 patients with childhood ALL and 266 healthy controls, and rs2910164 genotypes were determined by the polymerase chain reaction-restriction fragment length polymorphism methodology. Results: The allele G was associated with decreased childhood ALL risk (OR=0.66, 95%CI=0.52-0.85, p=0.0011). Consistently, the GG genotype was associated with a decreased susceptibility (OR=0.40, 95%CI=0.23-0.67, p=0.0004). Patients with CG and GG genotypes were of earlier onset than those with CC genotype (p=0.0255 and p=0.0001). Conclusion: MiR146a rs2910164 G allele serves as a protective marker for childhood ALL in Taiwan.

The neodymium-doped yttrium aluminum garnet (Nd-YAG) laser is used for removal of pigmented skin patches and rejuvenation of skin. However, complications such as hyperpigmentation, hypopigmentation, and petechiae can occur after frequent treatments. Therefore, identifying the risk factors for such complications is important. The development of a multivariable logistic regression model with least absolute shrinkage and selection operator (LASSO) is needed to provide valid predictions about the incidence of post inflammatory hyperpigmentation complication probability (PIHCP) among patients treated with Nd-YAG laser toning. A total of 125 female patients undergoing laser toning therapy between January 2014 and January 2016 were examined for post-inflammatory hyperpigmentation (PIH) complications. Factor analysis was performed using 15 potential predictive risk factors of PIH determined by a physician. The LASSO algorithm with cross-validation was used to select the optimal number of predictive risk factors from the potential factors for a multivariate logistic regression PIH complication model. The optimal number of predictive risk factors for the model was five: immediate endpoints of laser (IEL), &alpha, hydroxy acid (AHA) peels, Fitzpatrick skin phototype (FSPT), acne, and melasma. The area under the receiver operating characteristic curve (AUC) was 0.79 (95% CI, 0.70&ndash, 0.88) in the optimal model. The overall performance of the LASSO-based PIHCP model was satisfactory based on the AUC, Omnibus, Nagelkerke R2, and Hosmer&ndash, Lemeshow tests. This predictive risk factor model is useful to further optimize laser toning treatment related to PIH. The LASSO-based PIHCP model could be useful for decision-making.

Few studies have examined the contribution of matrix metalloproteinases (MMP) to either diagnosis or prognosis of pterygium. The aim of this study was to investigate the contribution of MMP-1 genotypes to pterygium risk.A total of 134 cases and 268 controls were included and their MMP-1 -1607 (rs1799705) genotypes were examined by polymerase chain reaction-restriction fragment length polymorphism.The percentages of 2G/2G, 1G/2G, and 1G/1G for rs1799705 genotypes were 48.5, 36.6 and 14.9% among patients and 33.9, 44.8, and 21.3% among controls (p trend=0.0167). The odds ratios (ORs) after adjusting for age and gender for 1G/2G and 1G/1G genotypes at rs1799705 were 0.54 (95%CI=0.33-0.89, p=0.0168) and 0.46 (95%CI=0.27-0.88, p=0.0192), respectively. Consistently, the adjusted OR for those carrying the 1G allele at MMP-1 -1607 was 0.61 (95%CI=0.41-0.78, p=0.0167), compared with the wild-type 2G allele.The genotypes at rs1799705 play a role in determining personal susceptibility to pterygium.