Validation and comparison of prognostic scoring systems in patients with head and neck squamous cell carcinoma treated with nivolumab.

OBJECTIVE: Several scoring systems have been developed to predict prognosis in patients with refractory cancer. We aimed to validate eight scoring systems and determine the best method for predicting the prognosis of head and neck squamous cell carcinoma treated with nivolumab. METHODS: This multicentre retrospective study involved 154 patients with recurrent and/or metastatic head and neck squamous cell carcinoma treated with nivolumab between 2017 and 2020. Oncological outcomes were assessed according to the scoring systems, including MD Anderson Cancer Center + neutrophil-to-lymphocyte ratio and Hammersmith scores. Objective response, overall survival and progression-free survival were evaluated using logistic regression and Cox proportional hazards analyses. Receiver operating curve analysis was used to calculate the area under the curve and estimate the efficacy of each score. RESULTS: No significant associations were found between the responses and any score. Seven of the eight scoring systems were associated with disease control (odds ratio, 0.26-0.70). Amongst the eight scoring systems, MD Anderson Cancer Center + neutrophil-to-lymphocyte ratio showed the highest area under the curve for predicting response and disease control. Seven scoring systems were prognostic factors for progression-free survival (hazard ratio, 1.22-1.95). All eight scoring systems were prognostic factors for overall survival (hazard ratio, 1.62-3.83). According to the time-dependent receiver operating characteristics analysis for overall survival, the Hammersmith scoring system had the best predictive ability at 3 months, and the MD Anderson Cancer Center + neutrophil-to-lymphocyte ratio scoring system had the highest area under the curve between 6 and 24 months. CONCLUSIONS: MD Anderson Cancer Center + neutrophil-to-lymphocyte ratio and Hammersmith scoring systems were better predictors of prognosis in patients with head and neck squamous cell carcinoma treated with nivolumab.

Association of circulating tumor HPV16DNA levels and quantitative PET parameters in patients with HPV-positive head and neck squamous cell carcinoma.

Circulating tumor DNA (ctDNA), which circulates in the blood after being shed from cancer cells in the body, has recently gained attention as an excellent tumor marker. The purpose of this study was to evaluate whether ct human papillomavirus (HPV) 16 DNA (ctHPV16DNA) levels were associated with quantitative PET parameters in patients with HPV-positive head and neck (HN) squamous cell carcinoma (SCC). Fifty patients with oropharyngeal SCC (OPSCC) and 5 with SCC of unknown primary (SCCUP) before treatment were included. They all underwent blood sampling to test ctHPV16DNA levels and FDG PET-CT examinations. Quantitative PET parameters included SUVmax, metabolic tumor volume (MTV), MTV of whole-body lesions (wbMTV), and 56 texture features. ctHPV16DNA levels were compared to texture features of primary tumors in OPSCC patients (Group A) or the largest primary or metastatic lymph node lesions in OPSCC and SCCUP patients (Group B) and to other PET parameters. Spearman rank correlation test and multiple regression analysis were used to confirm the associations between ctHPV16DNA levels and PET parameters. ctHPV16DNA levels moderately correlated with wbMTV, but not with SUVmax or MTV in Groups A and B. ctHPV16DNA levels exhibited a weak negative correlation with low gray-level zone emphasis in Groups A and B. Multiple regression analysis revealed that wbMTV and high gray-level zone emphasis were the significant factors for ctHPV16DNA levels in Group B. These results were not observed in Group A. This study demonstrated that ctHPV16DNA levels correlated with the whole-body tumor burden and tumor heterogeneity visualized on FDG PET-CT in patients with HPV-positive HNSCC.

Circulating Plasma Exosomal PD-L1 Predicts Prognosis of Head and Neck Squamous Cell Carcinoma After Radiation Therapy.

Purpose: Radiation therapy is widely used to treat head and neck squamous cell carcinoma (HNSCC). This study evaluated the association between circulating plasma programmed death-ligand 1 (PD-L1) and the outcomes of patients with HNSCC after radiation therapy. Methods and Materials: In this retrospective observational study, plasma samples of 76 patients with HNSCC who underwent radiation therapy from June 2019 to August 2021 were analyzed. These plasma samples were obtained before radiation therapy. The median follow-up was 32.5 months. Total and exosomal PD-L1 was measured by enzyme-linked immunosorbent assay and retrospectively analyzed for association with overall survival (OS), progression-free survival (PFS), and local control (LC). Prognostic factors among patients' characteristics and circulating PD-L1 in plasma were evaluated by univariate (log-rank test) and multivariate (Cox proportional hazards model) analyses. Results: The median concentration of total PD-L1 in plasma was 115.1 pg/mL (95% CI, 114.7-137.9 pg/mL), and the median concentration of exosomal PD-L1 was 2.8 pg/mL (95% CI, 6.0-13.0 pg/mL). Univariate and multivariate analyses showed exosomal PD-L1 as a prognostic factor for PFS and LC. Patients with high exosomal PD-L1 in plasma had poor PFS and LC compared with those with low exosomal PD-L1, indicating that 1-year PFS was 79.2% versus 33.3% (P < .001) and 1-year LC was 87.3% versus 50.0% (P < .001) in patients with high and low exosomal PD-L1, respectively. However, exosomal PD-L1 in plasma had no significant effect on OS. Total PD-L1 in plasma did not correlate with PFS, LC, and OS. Conclusions: The pretreatment circulating exosomal PD-L1 in plasma of patients with HNSCC was a prognostic factor after radiation therapy.

Prognostic significance of nutritional indices in patients with head and neck squamous cell carcinoma treated with immune checkpoint inhibitors.

BACKGROUND: Although patients with head and neck squamous cell cancer (HNSCC) often show malnutrition, its effects on immune checkpoint inhibitor (ICI) treatment outcomes in these patients are unclear. OBJECTIVES: To investigate the prognostic influence of nutritional indices in patients with HNSCC treated with ICIs and determine the optimal indices. METHODS: This retrospective study included 106 patients with HNSCC treated with ICIs between 2017 and 2022. The prognostic influences of body mass index (BMI), geriatric nutritional risk index (GNRI), and prognostic nutritional index (PNI) on overall survival (OS) and progression-free survival (PFS) were analysed using the Kaplan-Meier method and Cox-regression models. RESULTS: The 1-year PFS rates in the groups with high and low BMI, GNRI, and PNI were, respectively, 24.2% and 28.4% (p = .731), 29.7% and 14.4% (p = .024), and 30.3% and 13.9% (p = .015). PNI was an independent prognostic factor for both PFS (hazard ratio (HR) = 1.89; 95% confidence interval (CI), 1.08-3.29) and OS (HR = 3.26; 95% CI, 1.66-6.40). CONCLUSIONS: PNI can predict ICI outcomes and should be assessed when ICI treatment is considered.

Outpatient ablation treatment with two doses of 30 mCi of radioactive iodine for non-low-risk papillary thyroid cancer.

Outpatient ablation therapy with low-dose radioactive iodine (RAI) is applied to non-low-risk papillary thyroid cancer patients due to a chronic shortage of inpatient RAI treatment wards in Japan. We used the maximum dosage available for outpatient therapy of 30 mCi of RAI for ablation and diagnostic (Dx) whole-body scintigraphy (WBS). This study aimed to examine the significance of the second dose of 30 mCi. DxWBS was performed 6 months after ablation, and assessment of success or failure was performed 12 months after ablation. A second WBS was performed in the remaining RAI accumulation cases in the neck on DxWBS. The criteria for successful ablation was negative cervical accumulation on WBS, thyroid stimulating hormone-suppressed thyroglobulin (sup-Tg) below 1.0 ng?/?mL, and no increase in thyroglobulin antibody (TgAb) level. At the time of DxWBS, 35?/?68 cases met the successful criteria, and 45 cases achieved success at assessment. Sup-Tg values decreased significantly after ablation and decreased further after DxWBS in successful ablation cases, whereas those were not changed in ablation failure cases. Findings indicated that RAI used in DxWBS had therapeutic effects. It makes sense to use 30 mCi for DxWBS, given the current difficulty of inpatient ablation therapy with high-dose RAI. J. Med. Invest. 70 : 17-21, February, 2023.

Clearance Profile of Circulating Tumor Human Papillomavirus DNA During Radiotherapy Predicts Clinical Outcomes in Human Papillomavirus-Related Oropharyngeal Cancer.

PURPOSE: This study aimed to examine whether circulating tumor human papillomavirus type 16 (HPV16) DNA (ctHPV16DNA) can help identify patients with locally advanced HPV16-related oropharyngeal squamous cell carcinoma who may benefit from deintensified treatment. MATERIALS AND METHODS: We serially collected blood samples before, during, and after treatment from 22 patients who received 70 Gy radiotherapy alone and longitudinally quantified ctHPV16DNA using droplet digital polymerase chain reaction. We correlated the clearance profile of ctHPV16DNA with clinical outcomes. RESULTS: The percentage of patients with detectable ctHPV16DNA decreased after every 10 Gy of radiotherapy. By contrast, the percentage of patients who later developed treatment failure among patients with detectable ctHPV16DNA gradually increased as radiotherapy proceeded, reaching 100% after 60 Gy of radiotherapy. We defined patients with and without detectable ctHPV16DNA after receiving 40 Gy as having slow and rapid clearance profiles, respectively. All 12 patients with a rapid clearance profile remained disease-free after radiotherapy. Of the 10 patients with a slow clearance profile, three had persistent or progressive disease at response evaluation after radiotherapy and one developed distant metastasis during follow-up (ie, four patients experienced treatment failure). The median follow-up for surviving patients was 38.6 months, and the 3-year failure-free survival rates of patients with rapid and slow clearance profiles were 100% and 58%, respectively (P = .02). Neither baseline ctHPV16DNA levels nor metabolic tumor volume was an independent predictor of the pattern of the clearance profile. CONCLUSION: In patients with HPV16-related oropharyngeal squamous cell carcinoma receiving radiotherapy, a slow ctHPV16DNA clearance profile could prelude unfavorable outcomes. Monitoring ctHPV16DNA is essential for determining the clearance profile, which might help optimize treatment intensity individually.

Distant metastasis in head and neck squamous cell carcinoma variants: A population-based study.

BACKGROUND: Head and neck squamous cell carcinoma (HNSCC) with distant metastasis (DM) has poor prognosis. HNSCC has several histological variants with varying characteristics. We investigated the DM rates and prognoses of patients with DM among the HNSCC variants. METHODS: We obtained data from 54 722 cases using the Surveillance, Epidemiology, and End Results database. Odds ratios (ORs) for DM and hazard ratios (HRs) for overall survival (OS) were estimated using a logistic regression model and a Cox proportional hazard model, respectively. RESULTS: DM rate was the lowest in verrucous carcinoma and the highest in basaloid squamous cell carcinoma (BSCC) (0.2% and 9.4%, respectively). ORs for DM were 3.63 for adenosquamous carcinoma, 6.80 for BSCC, and 3.91 for spindle cell carcinoma (SpCC). SpCC was significantly associated with a poor OS (HR, 1.61). CONCLUSIONS: DM rates differed among the HNSCC variants. The prognosis of metastatic SpCC is worse than that of other metastatic HNSCCs.

Early-stage glottic cancer of rare squamous cell carcinoma variants: a population-based study.

BACKGROUND: Squamous cell carcinoma (SCC) is the most common histological type of laryngeal cancer. Several variants of SCC have been reported. However, how these variants differ from conventional SCC and how they should be treated remain to be elucidated. OBJECTIVE: To compare the prognosis of early-stage glottic cancer among SCC variants. METHODS: We obtained data from 12471 cases using the Surveillance, Epidemiology, and End Results database. Disease-specific survival (DSS) and overall survival (OS) rates were estimated using the Kaplan-Meier method. A Cox proportional hazard model was used to estimate hazard ratios (HRs) according to the variants. RESULTS: HRs for DSS and OS compared with well-differentiated SCC were 3.83 and 3.48 for adenosquamous, 1.42 and 1.42 for basaloid, 1.14 and 1.17 for papillary, 0.85 and 0.94 for spindle, and 0.81 and 1.00 for verrucous SCC. The difference in DSS among the treatment modalities was significant in conventional and papillary SCC (p < .001 and p = .032, respectively). CONCLUSIONS: The prognosis of SCC variants, except for adenosquamous SCC, is comparable to that of conventional SCC.

Radiation vs surgery for early-stage laryngeal verrucous carcinoma: A population-based propensity score matched-study.

BACKGROUND: Verrucous carcinoma (VC) is a rare variant of squamous cell carcinoma. Although VC is considered radioresistant, concrete evidence for this is absent. METHODS: We obtained data on VC treated with surgery or radiation from the Surveillance, Epidemiology, and End Results database. Treatment selection bias was reduced by propensity score matching. Overall survival (OS) and disease-specific survival (DSS) rates were estimated using the Kaplan-Meier method. Hazard ratios (HRs) were estimated using Cox proportional hazards models. RESULTS: Five-year OS rates in the radiation and surgery groups were 72.7% and 72.0%, respectively (P = 0.111); five-year DSS rates in the same were 86.7% and 88.4%, respectively (P = 0.234). HRs of radiation compared with surgery were 1.68 (95% confidence interval (CI), 0.96-2.95) for OS and 1.95 (95% CI, 0.69-5.53) for DSS. CONCLUSIONS: Similar prognoses were observed in patients with VC treated with radiation and surgery. VC can be treated using radiation.

Predictive significance of body composition indices in patients with head and neck squamous cell carcinoma treated with nivolumab: A multicenter retrospective study.

BACKGROUND: The identification of predictive factors is imperative for identifying patients with optimal responses to nivolumab. We aimed to determine whether body composition parameters can predict treatment outcomes in patients with head and neck squamous cell carcinoma (HNSCC) treated with nivolumab. METHOD: We performed a multicenter retrospective chart review of patients with recurrent and/or metastatic HNSCC treated with nivolumab between 2017 and 2020. Computed tomography images and anthropometric measures were used to determine the skeletal muscle index (SMI), subcutaneous adipose index, visceral adipose index (VAI), and body mass index. Objective response, overall survival (OS), progression-free survival (PFS), and severe immune-related adverse events (irAEs) were the main outcomes. Odds ratios (ORs) and hazard ratios (HRs) for low-index groups compared with high-index groups were calculated for these outcomes. RESULTS: Our study comprised 114 patients with a median follow-up period of 23.1 months. Low SMI and low VAI were significantly associated with poor disease control [OR: 0.39, 95% confidence interval (CI): 0.15-0.97] and poor response (OR: 0.38, 95% CI: 0.15-0.94), respectively. Low SMI independently predicted poor OS (HR: 2.06, 95% CI: 1.16-3.67), poor PFS (HR: 1.74, 95% CI: 1.04-2.92), and increased incidence of irAEs (OR: 6.00, 95% CI: 1.04-34.61). Low VAI independently predicted poor PFS (HR 2.07, 95% CI: 1.15-3.73). CONCLUSION: The SMI and VAI are predictive factors of nivolumab therapy in patients with HNSCC. Body composition indices should be assessed before nivolumab treatment for achieving optimal responses to nivolumab.

Neutrophil-to-lymphocyte ratio as a prognostic marker for head and neck squamous cell carcinoma treated with immune checkpoint inhibitors: Meta-analysis.

We investigated the prognostic impact of the neutrophil-to-lymphocyte ratio (NLR) in patients with head and neck squamous cell carcinoma (HNSCC) treated with immune checkpoint inhibitors (ICIs). We systematically searched electronic databases and identified articles reporting an association between NLR and treatment results in patients with HNSCC treated with ICIs. Hazard ratios (HRs) for overall survival (OS) and progression-free survival (PFS) and odds ratios (ORs) for response and disease control were extracted. Pooled HRs and ORs were estimated using random-effects models. Fourteen studies involving 929 patients were included. A higher NLR was associated with poor OS (HR 2.03, 95% confidence interval [CI] 1.50-2.74), PFS (HR 2.15, 95% CI 1.44-3.21), response (OR 0.49, 95% CI 0.26-0.93), and disease control (OR 0.30, 95% CI 0.12-0.74). The NLR predicts treatment results with ICIs in patients with HNSCC.

Performance of oral HPV DNA, oral HPV mRNA and circulating tumor HPV DNA in the detection of HPV-related oropharyngeal cancer and cancer of unknown primary.

A biomarker that is useful for the detection of human papillomavirus (HPV)-related oropharyngeal cancer (OPC) and cancer of unknown primary (CUP) is indispensable. We evaluated the diagnostic performance of HPV DNA and mRNA in oral gargle samples and circulating tumor HPV16 DNA (ctHPV16DNA) in blood samples. Oral HPV DNA and mRNA were analyzed using commercially available HPV assays of the GENOSEARCH HPV31 and Aptima, respectively. ctHPV16DNA was analyzed using in-house droplet digital polymerase chain reaction. Seventy-four patients with OPC and eight patients with CUP were included. The sensitivity and specificity of oral HPV DNA, oral HPV mRNA, and ctHPV16DNA were 82% (95% confidence interval [CI] = 66-92) and 100% (95% CI = 88-100), 85% (95% CI = 69-94) and 94% (95% CI = 73-100), and 93% (95% CI = 81-99) and 97% (95% CI = 84-100), respectively, for HPV16-related OPC, while those were 20% (95% CI = 1-72) and 100% (95% CI = 3-100), 0% (95% CI = 0-52) and 100% (95% CI = 3-100), and 100% (95% CI = 54-100) and 100% (95% CI = 16-100), respectively, for HPV16-related CUP. The sensitivity of ctHPV16DNA for HPV16-related OPC was higher than that of oral biomarkers, though the difference was not statistically significant. ctHPV16DNA remarkably correlated with the anatomic extent of disease, total metabolic tumor volume and HPV16 copy number per tumor genome in patients with HPV16-related OPC/CUP, whereas oral biomarkers did not. In conclusion, ctHPV16DNA is a potentially promising biomarker for HPV16-related OPC, while further studies are required for HPV16-related CUP.

Prognostic impact of sarcopenia in patients with head and neck cancer treated with surgery or radiation: A meta-analysis.

BACKGROUND: The objective of this study was to compare the prognostic impact of sarcopenia in patients with head and neck cancer (HNC) treated with surgery or radiation. METHODS: We systematically searched electronic databases to identify articles reporting the impact of sarcopenia on the prognosis of patients with HNC. Hazard ratios (HRs) and 95% confidence intervals (CIs) for overall survival (OS), disease-free survival (DFS), and disease-specific survival (DSS) were extracted and pooled. HR according to treatment modality were estimated using random-effects models. Statistical analyses were carried out using the Comprehensive Meta-Analysis software. RESULTS: In total, 18 studies enrolling 3,233 patients were included. Sarcopenia was associated with poor OS in both surgery and radiotherapy groups (hazard ratio [HR] 2.50, 95% confidence interval [CI] 1.95-3.21; HR 1.63, 95% CI 1.40-1.90, respectively). The HR was significantly higher in the surgery group than in the radiotherapy group (p = 0.004), with similar results obtained for DFS (HR 2.59, 95% CI 1.56-4.31; HR 1.56, 95% CI 1.24-1.97 for the surgery and radiotherapy groups, respectively) and DSS (HR 2.96, 95% CI 0.73-11.95; HR 2.67, 95% CI 1.51-4.73 for the surgery and RT groups, respectively). CONCLUSIONS: Sarcopenia was a poor prognostic factor for HNC, regardless of the treatment modality. However, the adverse effects of sarcopenia on survival were more prominent in the surgery group than in the radiotherapy group. Sarcopenia assessment is required for appropriate treatment decision-making.

Predictive impact of sarcopenia in solid cancers treated with immune checkpoint inhibitors: a meta-analysis.

Sarcopenia, which is characterized by a decrease in muscle quantity or quality, is commonly observed in patients with cancer. Recent research has reported contradictory results on the association between sarcopenia and the efficacy of immune checkpoint inhibitors (ICIs). We conducted a systematic review and meta-analysis to investigate this discrepancy. We systematically searched three electronic databases to identify articles reporting on the association between sarcopenia and treatment outcomes in patients with solid cancers who received ICIs. The outcomes assessed were hazard ratios (HRs) for overall survival (OS) and progression-free survival (PFS), and odds ratios (ORs) for objective response rate (ORR), disease control rate (DCR), and toxicity. Pooled estimates and their 95% confidence intervals (CIs) were calculated. A total of 2501 patients from 26 studies were analysed. Sarcopenia was observed in 44.7% (95% CI: 38.2-51.3) of the patients and was significantly associated with poor survival (HR = 1.55, 95% CI = 1.32-1.82 for OS and HR = 1.61, 95% CI = 1.35 to 1.93 for PFS). The HRs (95% CIs) for OS according to the diagnostic measures used were 1.97 (0.88-4.41) for psoas muscle index (PMI), 1.41 (0.87-2.28) for skeletal muscle density (SMD), and 1.43 (1.23-1.67) for skeletal mass index (SMI). The HRs (95% CIs) for PFS were 1.86 (1.08-3.21) for PMI, 1.27 (0.94-1.71) for SMD, and 1.38 (1.11-1.71) for SMI. Poor radiological response to ICI therapy was observed in patients with sarcopenia (OR = 0.52, 95% CI = 0.34-0.80 for ORR and OR = 0.45, 95% CI = 0.30-0.67 for DCR). The ORs for ORR (95% CIs) were 0.56 (0.15-2.05) for PMI and 0.78 (0.56-1.09) for SMI. The oncologic outcomes associated with melanoma and non-small cell lung cancer (NSCLC) were comparable with those observed overall (HR for OS = 2.02, 95% CI = 1.26-3.24 for melanoma and HR for OS = 1.61, 95% CI = 1.19-2.18 for NSCLC). In contrast, the occurrence of severe toxicity was not associated with sarcopenia (OR = 1.13, 95% CI = 0.51-2.52). Poor survival and poor response in patients with sarcopenia indicate a negative association between sarcopenia and efficacy of ICIs. Sarcopenia's predictive ability is consistent across various tumour types. For the selection of patients who may respond to ICIs pre-therapeutically, the presence of sarcopenia should be assessed in clinical practice.

Modified TPEx as First-line Treatment for Recurrent and/or Metastatic Head and Neck Cancer.

BACKGROUND/AIM: To retrospectively evaluate the efficacy and safety of modified TPEx (docetaxel 60 mg/m2 on day 1, cisplatin 60 mg/m2 on day 1, and weekly cetuximab 250 mg/m2 with loading dose of 400 mg/m2) followed by maintenance cetuximab as first-line treatment for inoperable recurrent and/or metastatic squamous cell carcinoma of the head and neck. PATIENTS AND METHODS: We analyzed 22 Japanese patients receiving modified TPEx every 21 days for four cycles with or without prophylactic granulocyte colony-stimulating factor (G-CSF). RESULTS: The best overall response rate was 55% [95% confidence interval (CI)=35-73]. The median progression-free survival and overall survival were 8.9 months (95%CI=3.9-10.2) and 14.3 months (95%CI=10.1-28.2), respectively. Without prophylactic G-CSF, Grade 3/4 neutropenia and febrile neutropenia was common (94% versus 20%; p=0.003 and 41% versus 0%; p=0.11, respectively). CONCLUSION: The modified TPEx is effective, while prophylactic G-CSF is essential.

Radiation Therapy Alone for Human Papillomavirus-Related Squamous Cell Carcinoma of the Oropharynx: A Single-Arm, Phase 2 Study.

PURPOSE: Human papillomavirus (HPV)-related squamous cell carcinoma of the oropharynx (OPSCC) is extremely radiosensitive. Radiation therapy plus high-dose cisplatin remains the standard of care but causes long-term toxicity. Treatment deintensification approaches that reduce toxicity while maintaining survival are desirable for HPV-related OPSCC. METHODS AND MATERIALS: We conducted a single-arm, multicenter, phase 2 trial. Patients with newly diagnosed, biopsy-proven, American Joint Committee on Cancer (seventh edition) stage III or IV OPSCC positive for both p16 and HPV DNA were eligible. Patients with T4, N3, or T1N1 disease were excluded. Smoking history was not included in eligibility criteria. Patients received intensity modulated radiation therapy (IMRT) of 70 Gy in 35 fractions or 70.4 Gy in 32 fractions without chemotherapy. The primary endpoint was complete response or complete metabolic response 10 weeks after IMRT completion. RESULTS: Between September 13, 2013, and November 15, 2016, 39 patients were enrolled according to a 2-stage Simon design. Twenty-three patients (59%) had smoked for more than10 pack-years. Thirty-six patients (92%) had tumors genotyped as HPV16. Thirty-seven patients (95%) received full-dose radiation therapy and 35 (90%) had complete response or complete metabolic response. Median follow-up was 51 months (interquartile range, 41-63 months). One patient (3%) had regional recurrence and 3 (8%) had distant metastasis. One patient died of disease. The 2-year progression-free survival rate was 94% (95% CI, 81%-99%), and the 2-year overall survival rate was 100%. Common grade 3 adverse events during IMRT included mucositis in 10 patients (26%) and dysphagia in 7 patients (18%). No patients were dependent on a feeding tube at 1 month after IMRT completion. No grade 3 or 4 late adverse events were observed. CONCLUSIONS: IMRT alone is associated with excellent response as well as reduced toxicity and could be a treatment option for carefully selected patients with locally advanced "true" HPV-related OPSCC. Further studies are warranted.

Clinical significance of cervical and ocular vestibular evoked myogenic potentials in benign paroxysmal positional vertigo: a meta-analysis.

PURPOSE: As the pathological cause of benign paroxysmal positional vertigo (BPPV), the dislocation or degeneration of otoconia in the utricle and saccule is suggested. Vestibular evoked myogenic potential (VEMP) could reflect otolithic dysfunction due to these etiologies of BPPV. The aim of this study was to validate the clinical significance of cervical (c) and ocular (o) VEMP in BPPV by a meta-analysis of previous articles. METHODS: Articles related to BPPV with data on cVEMP and oVEMP were collected. The following keywords were used to search PubMed and Scopus for English language articles: benign paroxysmal positional vertigo or BPPV and vestibular evoked myogenic potential or VEMP. RESULTS: The p13 latency in cVEMP and n1 latency in oVEMP were slightly but significantly prolonged in BPPV patients compared to control patients. AR in oVEMP of BPPV patients also showed higher value than that of control patients. However, the n23 latency and AR in cVEMP and p1 latency in oVEMP showed no significant difference between BPPV and control patients. Furthermore, latencies in VEMPs also showed no significant difference between an affected and a non-affected ear in BPPV patients. CONCLUSIONS: Our results indicated that otolith dysfunction of BPPVs was detected by latencies in VEMPs, and AR in oVEMP more sensitively reflects the difference between affected and non-affected ears in BPPV patients. The otolith dysfunction of BPPV might be induced by the systemic condition. However, the differences of latencies between BPPV patients and control patients were too small to use VEMPs as a prognostic predictor.

Neutrophil-to-Lymphocyte Ratio and Platelet-to-Lymphocyte Ratio as Prognostic Hematologic Markers of Bell's Palsy: A Meta-analysis.

OBJECTIVE: Bell's palsy (BP) is the most common cause of unilateral peripheral facial paralysis, and inflammation has been proposed as the main pathological cause. The study aim was to investigate the relationship between hematologic inflammatory markers, including the neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR), and BP. DATA SOURCES: The following key words were used to search PubMed and Scopus for English language articles: Bell's palsy, facial palsy, facial paresis or facial paralysis, neutrophil, lymphocyte, and platelet. STUDY SELECTION: Articles related to BP with NLR or PLR data. DATA EXTRACTION: The data included patient profiles, House-Brackmann score, treatment modality, NLR, and PLR. DATA SYNTHESIS: Seven articles were selected. A random effect model was used to analyze the aggregated data. Six of these articles that included the NLR and two that included the PLR of BP and control patients were analyzed for the difference between BP and control patients. Three articles that included the NLR of the recovery and nonrecovery groups were analyzed for the relationship between NLR and recovery. CONCLUSIONS: The NLR was significantly higher for the BP patients than for the controls. Furthermore, the NLR was significantly lower for the recovery group than for the nonrecovery group. A high NLR was associated with poor prognosis and related to the severity of facial nerve inflammation. There was no significant difference between the PLRs of the BP patients and controls. The NLR, but not the PLR, was found to be a useful prognostic indicator of BP.

Sphenopalatine artery surgery for refractory idiopathic epistaxis: Systematic review and meta-analysis.

OBJECTIVES: Epistaxis, especially posterior epistaxis, is occasionally refractory to treatment. In these cases, sphenopalatine artery surgeries, including cauterization and ligation, are required. Previous reports have demonstrated treatment results for these procedures but failed to provide high-level evidence. The aim of this study was to quantify the rates of failure and perioperative complications of these procedures by using a meta-analysis technique. METHODS: We systematically searched electronic databases and identified articles regarding epistaxis, sphenopalatine artery ligation, or cauterization. Pooled rebleeding and complication rates were calculated by using a random effects model. RESULTS: A total of 896 cases of sphenopalatine ligation or cauterization for epistaxis were analyzed. Pooled rebleeding rates for the entire cohort, cauterization group, and ligation group were 13.4% (95% confidence interval [CI] 10.0-17.8, P < 0.001), 7.2% (95% CI 4.6-11.0, P < 0.001), and 15.1% (95% CI 9.8-22.5, P < 0.001), respectively. Pooled perioperative complication rates for the entire cohort, cauterization group, and ligation group were 8.7% (95% CI 4.9-15.1, P < 0.001), 10.2% (95% CI 3.8-24.5, P < 0.001), and 6.4% (95% CI 1.8-20.9, P < 0.001), respectively. CONCLUSION: Overall, sphenopalatine surgery for refractory epistaxis is an effective method because of its low rates of failure and complications. Cauterization is more effective than ligation, whereas complications are comparable between the two procedures. Laryngoscope, 129:1731-1736, 2019.

Serum Fibrinogen as a Prognostic Factor in Sudden Sensorineural Hearing Loss: A Meta-analysis.

OBJECTIVE: High blood viscosity has been proposed as a mechanism for sudden sensorineural hearing loss (SSNHL); however, the relationship between blood markers of fibrinolysis or coagulation and severity or prognosis of SSNHL is still unclear. The aim of this study is to investigate the relationship between serum fibrinogen and SSNHL. DATA SOURCES: PubMed and Scopus were searched for English language articles using the following keywords: SSNHL, sudden hearing loss, sudden deafness, idiopathic hearing loss or idiopathic sensorineural hearing loss, and fibrinogen. STUDY SELECTION: The articles in the study related to SSNHL and provided data about the serum fibrinogen level. DATA EXTRACTION: The data included patient profiles, fibrinogen level, recovery, and treatment modality. DATA SYNTHESIS: Nineteen articles were selected. The aggregated data were analyzed using the random effect model. Two articles that included the fibrinogen level with recovery rates were analyzed for the relationship between the fibrinogen level and recovery. CONCLUSIONS: The average fibrinogen level was 318 ±â€Š8.5 mg/dl (mean ±â€Šstandard error, within normal range). There was no difference in the fibrinogen level between SSNHL patients and the control group. The fibrinogen level of the recovery group was lower than that of the no recovery group. This showed that a high fibrinogen level was associated with poor prognosis, and it could be related to the severity of the pathological change rather than being the cause of the SSNHL. SSNHL includes various pathologies; therefore, the appropriate therapy should be selected based on each condition.