Purpose: Precision oncology approach for recurrent and metastatic head and neck squamous cell carcinoma (HNSCC) is necessary due to its dismal prognosis. We performed a genomic profile-based umbrella trial of patients with platinum-refractory HNSCC (KCSG-TRIUMPH). Here, we present an in-depth report of the the nintedanib arm (arm 3) of the current trial. Materials and Methods: The TRIUMPH study was a multicenter, open-label, single-arm phase 2 trial, in which patients were assigned to treatment arms based on next-generation sequencing (NGS)–based, matching genomic profiles. Patients whose tumors harbor fibroblast growth factor receptor (FGFR) alteration were enrolled in the nintedanib arm (arm 3) as part of the TRIUMPH study. The primary endpoint was the overall response rate (ORR), and secondary endpoints included overall survival (OS), progression-free survival (PFS), safety, and biomarker analysis. Results: Between October 2017 and August 2020, 207 were enrolled in the TRIUMPH study, and eight were enrolled in the nintedanib arm. ORR and disease control rate were 42.9% and 57.1%, respectively. The median PFS was 5.6 months and the median duration of response was 9.1 months. Median OS was 11.1 months. One patient maintained the partial response for 36 months. Overall, the toxicity profiles were manageable. Conclusion Single-agent nintedanib has demonstrated significant efficacy in FGFR-mutated, recurrent or metastatic HNSCC patients, with tolerable toxicity profiles. The results from the study have provided the basis for routine NGS screening and FGFR-targeted therapy. Because of the small number of patients due to slow accrual in this study, further studies with a larger cohort are warranted for statistical power.

Korean Society of Thyroid-Head and Neck Surgery appointed a Task Force to provide guidance on the implementation of a surgical treatment of oral cancer. MEDLINE databases were searched for articles on subjects related to “surgical management of oral cancer” published in English. Results were restricted to systematic reviews, randomized control trials/controlled clinical trials, and observational studies. The quality of evidence was rated with use RoBANS (Risk of Bias Assessment Tool for Nonrandomized Studies) and AMSTAR (A Measurement Tool to Assess the Methodological Quality of Systematic Reviews). Evidence-based recommendations for practice were ranked according to the American College of Physicians grading system. Additional directives are provided as expert opinions and Delphi questionnaire when insufficient evidence existed. The Committee developed 68 evidence-based recommendations in 34 categories intended to assist clinicians and patients and counselors, and health policy-makers. Proper surgical treatment selection for oral cancer, which is directed by patient- and subsite-specific factors, remains the greatest predictor of successful treatment outcomes. These guidelines are intended for use in conjunction with the individual patient's treatment goals.
Advisory Committees ; Bias (Epidemiology) ; Carcinoma, Squamous Cell ; Counseling ; Expert Testimony ; Humans ; Mouth Neoplasms ; Neck ; Republic of Korea

PURPOSE: To investigate the differences in treatment outcomes between two radiation techniques, intensity-modulated radiotherapy (IMRT) and three-dimensional conformal radiotherapy (3DCRT).MATERIALS AND METHODS: We retrospectively analyzed 160 (IMRT = 23, 3DCRT = 137) patients with stage I glottic cancer treated from January 2005 through December 2016. The IMRT was performed with TomoTherapy (16 patients), volumetric-modulated arc therapy (6 patients), and step-and-shoot technique (1 patient), respectively. The 3DCRT was performed with bilateral parallel opposing fields. The median follow-up duration was 30 months (range, 31 to 42 months) in the IMRT group and 65 months (range, 20 to 143 months) in the 3DCRT group.RESULTS: The 5-year overall survival and 3-year local control rates of the 160 patients were 95.7% and 91.4%, respectively. There was no significant difference in 3-year local control rates between the IMRT and 3DCRT groups (94.4% vs. 91.0%; p = 0.587). Thirteen of 137 patients in the 3DCRT group had recurrences. In the IMRT group, one patient had a recurrence at the true vocal cord. Patients treated with IMRT had less grade 2 skin reaction than the 3DCRT group, but this had no statistical significance (4.3% vs. 21.2%; p = 0.080).CONCLUSION: IMRT had comparable outcomes with 3DCRT, and a trend of less acute skin reaction in stage I glottic cancer patients
Follow-Up Studies ; Glottis ; Humans ; Laryngeal Neoplasms ; Radiotherapy, Conformal ; Radiotherapy, Intensity-Modulated ; Recurrence ; Retrospective Studies ; Skin ; Vocal Cords

PURPOSE: Pediatric-type sarcomas such as rhabdomyosarcoma (RMS), Ewing sarcoma (EWS), primitive neuroectodermal tumor (PNET), and desmoplastic small round-cell tumor (DSRCT) are rare in adults, with limited studies on their prognosis and optimal treatment strategies. We aimed to examine the outcome of children and adult patients with RMS, EWS, PNET, and DSRCT and relevant prognostic factors. MATERIALS AND METHODS: We retrospectively reviewed 220 pediatric-type sarcoma patients at a single institution between 1985 and 2011. Comparisons were made in order to examine differences in demographics, disease characteristics, and survival. Survival analyses were performed using the Kaplan-Meier method with log-rank tests and Cox proportional hazards models. RESULTS: A total of 220 consecutive patients were identified at our institute. Median age was 15.6 years (range, 0 to 81 years) and there were 108 children (49%) and 112 adult patients (51%). According to histological classification, 106 patients (48.2%) had RMS, 60 (27.3%) had EWS, 50 (22.7%) had PNET, and 4 (1.8%) had DSRCT. With a median follow-up period of 6.6 years, the estimated median overall survival (OS) of all patients was 75 months (95% confidence interval [CI], 27.2 to 122.8 months) and median event-free survival (EFS) for all patients was 11 months (95% CI, 8.8 to 13.2 months). No significant difference in OS and EFS was observed between adults and children. In multivariate analysis, distant metastasis (hazard ratio [HR], 1.617; 95% CI, 1.022 to 2.557; p=0.040) and no debulking surgery (HR, 1.443; 95% CI, 1.104 to 1.812; p=0.012) showed independent association with worse OS. CONCLUSION: Metastatic disease and no surgical treatment are poor prognostic factors for OS among pediatric-type sarcomas for both adults and children.
Adult* ; Child* ; Classification ; Demography ; Desmoplastic Small Round Cell Tumor ; Disease-Free Survival ; Follow-Up Studies ; Humans ; Incidence* ; Multivariate Analysis ; Neoplasm Metastasis ; Neuroectodermal Tumors, Primitive ; Prognosis ; Proportional Hazards Models ; Retrospective Studies ; Rhabdomyosarcoma ; Sarcoma* ; Sarcoma, Ewing

BACKGROUND: Busulfan, an alkylating agent administered prior to hematopoietic stem cell transplantation, has a narrow therapeutic range and wide variability in metabolism. We developed a liquid chromatography-tandem mass spectrometry (LC-MS/MS) method for rapid and accurate quantification of plasma busulfan. METHODS: Busulfan was separated and detected using an LC system containing a C18 column equipped with MS/MS. The sample was eluted with a mobile phase gradient for a total run time of 10 min. Plasma busulfan concentration was quantified against a 6-point standard curve in a multiple reaction monitoring mode at mass-to-charge (m/z) 264.1 > 151.1. Precision, recovery, matrix effect, linearity, detection capability, carryover, and stability were evaluated. The range of plasma busulfan concentration was obtained by analyzing samples from 9 children receiving busulfan. RESULTS: The coefficients of variation of within-run and within-laboratory precision were all below 5%. Recoveries were all within the range of 100-105%. Linearity was verified from 0 to 5,000 ng/mL. Limit of detection and limit of quantification were 1.56 and 25 ng/mL, respectively. Carryover rate was within allowable limits. Plasma busulfan concentration was stable for 2 weeks at -20degrees C and -80degrees C, but decreased by 25% when the plasma was stored for 24 hr at room temperature, and by <5% in 24 hr at 4degrees C. The plasma busulfan concentrations were between 347 ng/mL and 5,076 ng/mL. CONCLUSIONS: Our method using LC-MS/MS enables highly accurate, reproducible, and rapid busulfan monitoring with minimal sample preparation. The method may also enable safe and proper dosage.
Busulfan/*blood/standards ; Child ; Child, Preschool ; *Chromatography, High Pressure Liquid/standards ; Hematopoietic Stem Cell Transplantation ; Humans ; Infant ; Quality Control ; Reference Standards ; *Tandem Mass Spectrometry/standards

PURPOSE: KAI1 COOH-terminal interacting tetraspanin (KITENIN) has been found to act as a promoter of metastasis in murine models of colon cancer and squamous cell carcinoma (SCC). The suppression of tumor progression and metastasis of established colon cancer in mice was observed after intravenous delivery of small interfering RNA (siRNA) targeting KITENIN. The purpose of this study was to investigate the efficacy of gene therapy targeting KITENIN in human head and neck SCC. MATERIALS AND METHODS: SNU-1041, a well-established human hypopharyngeal SCC cell line, was used. KITENIN expression in SNU-1041 was measured by Western blot analysis. The cells were prepared, maintained in culture dishes with media, and divided into two groups: the si-KITENIN group and the scrambled group (control). The siRNA targeting KITENIN (si-KITENIN) and scrambled DNA were transfected into the SNU-1041 cells in each group. The effect of gene therapy was compared by in vitro experiments to evaluate invasion, migration, and proliferation. RESULTS: KITENIN was strongly expressed in the SNU-1041 cells, and the number of invaded cells was reduced more in the si-KITENIN group than in the scrambled group (p<0.001). The speed for the narrowing gap, made through adherent cells, was lower in the si-KITENIN group (p<0.001), and the number of viable proliferating cells was reduced in the si-KITENIN group compared to the scrambled group (p<0.001, the third day). KITENIN protein expression was no longer identified in the si-KITENIN group. CONCLUSION: Gene therapy using an anti-KITENIN strategy might be effective for head and neck squamous carcinoma.
Carcinoma, Squamous Cell/genetics/pathology/*therapy ; Carrier Proteins/*antagonists & inhibitors/genetics ; Cell Line, Tumor ; Cell Movement ; Cell Proliferation ; *Gene Therapy ; Head and Neck Neoplasms/genetics/pathology/*therapy ; Humans ; Membrane Proteins/*antagonists & inhibitors/genetics ; *RNA, Small Interfering

BACKGROUND AND OBJECTIVES: Firefighters face serious risks to their health and safety in the performance of their duties. In addition to the diverse occupational hazards well-known to the public, firefighters are also occasionally exposed to high levels of noise, such as sirens, horns, and electronic alerting signals. MATERIALS AND METHODS: We first measured the noise emitted by two fire trucks and one ambulance. Next, we enrolled 171 firefighters (164 males, seven females). We designated the employees of a private school as controls for the firefighter group. After selecting workers, including audiometric testing at 1,000 and 4,000 Hz, the groups were age- and gender-matched. Both groups were included separately for the right and left ears at pure-tone test frequencies at 1,000 and 4,000 Hz. We chose the better ear thresholds and analyzed the differences in hearing levels at each frequency and each age group between the firefighters and controls. RESULTS: The sound pressure levels of the siren in and out of an ambulance, the first fire truck, and the second fire truck were 99.3 dB (A) and 108.9 dB (A), 92.3 dB (A) and 108.3, and 78.8 dB (A) and 99.0 dB (A), respectively. At 4,000 Hz, the hearing threshold was significantly increased by work period (p<0.01). Each hearing threshold level was significantly higher than controls (p<0.01). CONCLUSIONS: Many of the noise sources produce sounds exceeding 90 dB (A), and some firefighters may be exposed for brief periods to levels that exceed 105-110 dB (A). The hearing threshold level in firefighters is higher than the general population and noise-induced hearing loss in firefighters is possible. In the future, consistent, effective, and long-standing implementation of hearing conservation programs are needed, and special health examinations for hearing levels in firefighters must be conducted.
Ambulances ; Animals ; Ear ; Electronics ; Electrons ; Enzyme Multiplied Immunoassay Technique ; Firefighters ; Fires ; Hearing ; Hearing Loss ; Hearing Loss, Noise-Induced ; Horns ; Humans ; Male ; Motor Vehicles ; Noise ; Noise, Occupational

BACKGROUND AND OBJECTIVES: Firefighters face serious risks to their health and safety in the performance of their duties. In addition to the diverse occupational hazards well-known to the public, firefighters are also occasionally exposed to high levels of noise, such as sirens, horns, and electronic alerting signals. MATERIALS AND METHODS: We first measured the noise emitted by two fire trucks and one ambulance. Next, we enrolled 171 firefighters (164 males, seven females). We designated the employees of a private school as controls for the firefighter group. After selecting workers, including audiometric testing at 1,000 and 4,000 Hz, the groups were age- and gender-matched. Both groups were included separately for the right and left ears at pure-tone test frequencies at 1,000 and 4,000 Hz. We chose the better ear thresholds and analyzed the differences in hearing levels at each frequency and each age group between the firefighters and controls. RESULTS: The sound pressure levels of the siren in and out of an ambulance, the first fire truck, and the second fire truck were 99.3 dB (A) and 108.9 dB (A), 92.3 dB (A) and 108.3, and 78.8 dB (A) and 99.0 dB (A), respectively. At 4,000 Hz, the hearing threshold was significantly increased by work period (p<0.01). Each hearing threshold level was significantly higher than controls (p<0.01). CONCLUSIONS: Many of the noise sources produce sounds exceeding 90 dB (A), and some firefighters may be exposed for brief periods to levels that exceed 105-110 dB (A). The hearing threshold level in firefighters is higher than the general population and noise-induced hearing loss in firefighters is possible. In the future, consistent, effective, and long-standing implementation of hearing conservation programs are needed, and special health examinations for hearing levels in firefighters must be conducted.
Ambulances ; Animals ; Ear ; Electronics ; Electrons ; Enzyme Multiplied Immunoassay Technique ; Firefighters ; Fires ; Hearing ; Hearing Loss ; Hearing Loss, Noise-Induced ; Horns ; Humans ; Male ; Motor Vehicles ; Noise ; Noise, Occupational

BACKGROUND AND OBJECTIVES: Efonidipine hydrochloride, an L- and T-type dual calcium channel blocker, is suggested to have a heart rate (HR)-slowing action in addition to a blood pressure (BP)-lowering effect. The aim of this study was to determine the effect of efonidipine on HR and BP in patients with mild-to-moderate hypertension. SUBJECTS AND METHODS: In a multi-center, prospective, open-labeled, single-armed study, we enrolled 53 patients who had mild-to-moderate hypertension {sitting diastolic BP (SiDBP) 90-110 mmHg}. After a 2-week washout, eligible patients were treated with efonidipine (40 mg once daily for 12 weeks). The primary end point was the change in HR from baseline to week 12. The secondary end-point included the change in trough sitting BP and 24-hour mean BP between baseline and week 12. Laboratory and clinical adverse events were monitored at each study visit (4, 8, and 12 weeks). RESULTS: Fifty-two patients were included in the intention-to-treat analysis. After 12 weeks of treatment with efonidipine, the resting HR decreased significantly from baseline to week 12 {from 81.5+/-5.3 to 71.8+/-9.9 beats/minute (difference, -9.9+/-9.0 beats/minute), p<0.0001}. The trough BP {sitting systolic blood pressure (SiSBP) and SiDBP} and 24-hour mean BP also decreased significantly (SiSBP: from 144.6+/-8.2 to 132.9+/-13.5 mmHg, p<0.0001; SiDBP: from 96.9+/-5.4 to 88.3+/-8.6 mmHg, p<0.0001, 24-hour mean systolic BP: from 140.4+/-13.5 to 133.8+/-11.6 mmHg, p<0.0001; 24-hour mean diastolic BP: from 91.7+/-8.7 to 87.5+/-9.5 mmHg, p<0.0001). CONCLUSION: Efonidipine was effective in controlling both HR and BP in patients with mild-to-moderate hypertension.
Blood Pressure ; Calcium ; Calcium Channel Blockers ; Calcium Channels ; Dihydropyridines ; Heart ; Heart Rate ; Humans ; Hypertension ; Nitrophenols ; Organophosphorus Compounds ; Prospective Studies

OBJECTIVE: To investigate the musculoskeletal symptoms of migrant workers. We focused on the relationship between job stress and musculoskeletal symptoms. METHOD: A questionnaire was administered to 502 migrant workers who visited NGO migrant worker centers located in Gyung-gi province. A structured, self-reported questionnaire was administered to participants in order to capture the following information: sociodemographics, health factors including past medical history, work related characteristics, job stress, and musculoskeletal symptoms. The job stress questionnaires were used according to KOSS-26 and musculoskeletal symptoms were measured using KOSHA Code H-30-2003. We used multiple logistic regression analysis to assess the relationship between risk factors which included job stress, and musculoskeletal symptoms. RESULTS: The prevalence rate of musculoskeletal symptoms in survey subjects was 35.1%. Other than job stress factors, past medical history was the only factor that had a statistical relationship to musculoskeletal symptoms (P<0.01). In the domains of job stress, physical environment (OR 1.62, 95% CI: 1.03~2.54), job demand (OR 2.43, 95% CI: 1.46~4.03), job insecurity (OR 1.59, 95% CI: 1.03~2.47), occupational climate (OR 2.30, 95% CI: 1.27~4.19) were most likely experience musculoskeletal symptoms. CONCLUSION: The job stress factor appeared to correlate more with musculoskeletal symptoms than with sociodemographics or other factors. Hence, in order to prevent migrant worker's musculoskeletal symptoms, we believe that intervention in job stress (physical environment, job demand, job insecurity, occupational climate) is necessary.
Climate ; Humans ; Logistic Models ; Prevalence ; Questionnaires ; Risk Factors ; Transients and Migrants