Prophylactic Versus Reactive Megestrol Acetate Use for Critical Body Weight Loss in Patients with Pharyngeal and Laryngeal Squamous Cell Carcinoma Undergoing Concurrent Chemoradiotherapy.

This study compared the effects of megestrol acetate (MA) prophylactic (p-MA) versus reactive (r-MA) use for critical body-weight loss (>5% from baseline) during concurrent chemoradiotherapy (CCRT) in patients with advanced pharyngolaryngeal squamous cell carcinoma (PLSCC).Patients receiving CCRT alone in two phase-II trials were included for analyses. Both the p-MA and r-MA cohorts received the same treatment protocol at the same institution, and the critical body-weight loss, survival, and adverse event profiles were compared.The mean (SD) weight loss was 5.1% (4.7%) in the p-MA cohort (n = 54) vs. 8.1% (4.6%) in the r-MA cohort (n = 50) (p = .001). The percentage of subjects with body-weight loss >5% was 42.6% in the p-MA cohort vs. 68.0% in the r-MA cohort (p = .011). Tube feeding was needed in 22.2% of p-MA vs. 62.0% of r-MA patients (p < .001). Less neutropenia (26.0% vs. 70.0% [p < .001]) and a shorter duration of grade 3-4 mucositis (2.4 ± 1.4 vs. 3.6 ± 2.0 wk [p = .009]) were observed with p-MA treatment. Disease-specific survival, locoregional control, or distant metastasis-free survival did not differ. Less competing mortality from secondary primary cancer resulted in a better overall survival trend in the p-MA cohort.p-MA may reduce body-weight loss and improve adverse event profiles during CCRT for patients with PLSCC.

Factors impacting posttraumatic growth in head-and-neck cancer patients with oncologic emergencies.

PURPOSE: To identify factors associated with posttraumatic growth (PTG) of head-and-neck cancer squamous cancer (HNC) patients with oncologic emergencies (OE) within the first six months post-treatment. METHODS: We conducted a cross-sectional study of HNC patients in Taiwan from May 2019 to April 2021 using patient-reported outcomes. Patients were assessed for symptom distress, anxiety, fear of recurrence (FCR), and PTG. Multiple regression analysis was conducted to identify factors associated with PTG. The independent-samples t-test was used to compare PTG and its five specific domains in patients with low FCR, high FCR, low anxiety, and high anxiety. RESULTS: Of the 114 patients surveyed, 46.5% reported little-to-no PTG, and 53.5% had moderate-to-high PTG. Greater PTG was associated with greater FCR, longer time since OE, less anxiety, having a cancer recurrence, and greater educational attainment. These factors explained 38.6% of the variance in PTG. CONCLUSION: A notable proportion of HNC patients with OE-reported PTG but almost half-reported little-to-no PTG. PTG occurred most in the domain of appreciation of life. The study results also suggest that training patients in coping skills and inviting them to group growth experiences can help them increase PTG and cope with cancer-related psychological threats related to OE.

Treatment responses for branch retinal vein occlusion predicted by semi-automated fluorescein angiography quantification.

BACKGROUNDS: Branch retinal vein occlusion (BRVO) is one of the most important causes of visual loss in retinal vascular diseases. The aim of this study is to predict the treatment response of anti-vascular endothelial growth factor (anti-VEGF) therapy in BRVO using semi-automated quantified fluorescein angiography (FA) features. METHODS: This retrospective case-control study enrolled patients with BRVO who are receiving anti-VEGF therapy and have been followed up for > 1 year. Those receiving < 5 anti-VEGF injections in the first year were classified as the responsive group, while those receiving ≥5 injections were the refractory group. The FA images were subjected to semi-automated pre-processing. Fluorescein leakages at the 5-min image were represented by mean gray value over parafoveal and perifoveal regions. FA leakages and central retinal thickness (CRT) on optical coherence tomography (OCT) were used for predicting the treatment response and compared using area under receiver operating characteristic curve (AUC). RESULTS: Eighty-nine patients (56 males, 33 females, mean age 62.5 ± 10.9 years) with BRVO were enrolled. Of the 89 eyes, 47 (53%) were in the responsive group and 42 (47%) were in the refractory group. The refractory group had a significantly higher number of anti-VEGF injections in the first year (5.9 ± 1.6 versus 2.4 ± 1.2, p < 0.001) when compared with that of the responsive group. It had thicker pre-treatment CRT (p = 0.011), post-treatment best CRT (p < 0.001) and CRT at 1-year (p < 0.001). It also had a higher mean gray value over the parafoveal (p < 0.001) and the perifoveal (p < 0.001) regions. The mean gray value over perifoveal (AUC 0.846) and parafovel (AUC 0.818) had significantly larger AUC than that of the pre-treatment OCT (AUC 0.653; p = 0.005 and p = 0.016, respectively) when predicting treatment response. CONCLUSION: The refractory group had a more severe fluorescein leakage over the parafoveal and the perifoveal regions than the responsive group had. Semi-automated quantified FA leakage can be used as a biomarker for the prediction of anti-VEGF treatment response in macular edema due to BRVO.

A prospective nutritional assessment using Mini Nutritional Assessment-short form among patients with head and neck cancer receiving concurrent chemoradiotherapy.

BACKGROUND: No gold standard of nutritional assessment is established among patients with head and neck cancer (HNC) receiving concurrent chemoradiotherapy (CCRT). This study aimed to evaluate the clinical significance of pre-treatment nutritional status using the Mini Nutritional Assessment-short form (MNA-SF) among HNC patients receiving CCRT. METHODS: A total of 461 consecutive patients with newly diagnosed HNC treated with definitive CCRT at three medical institutes were prospectively enrolled. Nutritional status was assessed using MNA-SF within 7 days before CCRT initiation. Patients were classified as having normal nutrition, at risk of malnutrition, and malnourished groups according to MNA-SF for comparison. RESULTS: The 1-year overall survival rates were 89.8%, 76.8%, and 67.7% in the normal nutrition, at risk of malnutrition, and malnourished groups, respectively. Patients with normal nutrition had significantly lower rates of uncompleted radiotherapy and chemotherapy (4.5% and 4.1%, respectively) compared with patients at risk for malnutrition (14.1% and 11.5%, respectively) and those malnourished (11.1% and 11.1%, respectively). Patients with normal nutrition had significantly lower treatment-related complication rates regarding emergency room visits, hospital admission, and need for tubal feeding than those with at risk of malnutrition and malnourished. Patients with normal nutrition had significantly fewer severe hematologic toxicities (p = 0.044) and severe non-hematologic toxicities (p = 0.012) of CCRT than those malnourished. CONCLUSION: Pre-CCRT nutritional status identifies HNC patients vulnerable to treatment interruption and treatment complications. We suggest that nutritional assessment with MNA-SF should be incorporated in pre-CCRT evaluation for all HNC patients.

The association between immune-related adverse events and survival outcomes in Asian patients with advanced melanoma receiving anti-PD-1 antibodies.

BACKGROUND: The association between immune-related adverse events (irAEs) and survival outcomes in patients with advanced melanoma receiving therapy with immune checkpoint inhibitors (ICIs) has not been well established, particularly in Asian melanoma. METHODS: We retrospectively reviewed 49 melanoma patients undergoing therapy with ICIs (anti-PD-1 monotherapy), and analyzed the correlation between irAEs and clinical outcomes including progression-free survival (PFS) and overall survival (OS). RESULTS: Overall, the patients who experienced grade 1-2 irAEs had longer PFS (median PFS, 4.6 vs. 2.5 months; HR, 0.52; 95% CI: 0.27-0.98; p = 0.042) and OS (median OS, 15.2 vs. 5.7 months; HR, 0.50; 95% CI: 0.24-1.02; p = 0.058) than the patients who did not experience irAEs. Regarding the type of irAE, the patients with either skin/vitiligo or endocrine irAEs showed better PFS (median PFS, 6.1 vs. 2.7 months; HR, 0.40, 95% CI: 0.21-0.74; p = 0.003) and OS (median OS, 18.7 vs. 4.5 months; HR, 0.34, 95% CI: 0.17-0.69, p = 0.003) than patients without any of these irAEs. CONCLUSIONS: Melanoma patients undergoing anti-PD-1 monotherapy and experiencing mild-to-moderate irAEs (grade 1-2), particularly skin (vitiligo)/endocrine irAEs had favorable survival outcomes. Therefore, the association between irAEs and the clinical outcomes in melanoma patients undergoing anti-PD-1 ICIs may be severity and type dependent.

Femtosecond laser-assisted cataract surgery in a patient with traumatic cataract and corneal opacity after LASIK: a case report.

BACKGROUND: Femtosecond laser-assisted cataract surgery (FLACS) has been reported to reduce phacoemulsification time and energy compared to the manual phacoemulsification technique. This technique has been used in several complex cases such as zonular weakness, subluxated lens and traumatic cataracts because it causes less damage to weakened zonules. However, corneal opacity is considered a relative contraindication to FLACS, as it may interfere with laser beam delivery, thus causing unpredictable capsulorhexis and lens fragmentation/liquefaction. CASE PRESENTATION: We present here a case with traumatic cataract and corneal opacity after laser-assisted in situ keratomileusis (LASIK). The patient was successfully treated using FLACS, capsular tension ring and intraocular lens (IOL) implantation. Posterior capsule rupture and vitreous loss were noted during the operation. However, the intraocular lens was successfully captured because of a complete capsulorhexis performed by FLACS. CONCLUSION: This case report demonstrates that FLACS is a useful tool in selected patients with concurrent corneal opacity and traumatic cataract.

Response evaluation for immunotherapy through semi-automatic software based on RECIST 1.1, irRC, and iRECIST criteria: comparison with subjective assessment.

BACKGROUND: Pseudoprogression is difficult to diagnose in patients undergoing immunotherapy. Subjective response assessment is still common in clinical practice. PURPOSE: To evaluate the differences between response evaluation criteria in solid tumors version 1.1 (RECIST 1.1), immune-related response criteria (irRC), and modified RECIST 1.1 for immunotherapy (iRECIST) through semi-automatic software, and to compare iRECIST-based response evaluation with subjective assessment. MATERIAL AND METHODS: The best overall response of each patient based on RECIST 1.1, irRC, and iRECIST was determined on CT scans through semi-automatic software and the differences between the criteria were evaluated. Criteria-based response evaluation through semi-automatic software was compared with subjective assessment on radiology report by correlating the best overall response to overall survival. RESULTS: A total of 21 patients were included (five patients with melanoma, 12 patients with non-small-cell lung cancer, and four patients with hepatocellular carcinoma). Two patients with progressive disease by RECIST 1.1 but non-progressive disease by irRC and iRECIST eventually experienced tumor response and had favorable outcomes, indicating pseudoprogression. The survival difference between patients with non-progressive disease and progressive disease was better stratified through iRECIST-based response evaluation (P = 0.078) than that through subjective assessment (P = 0.501). CONCLUSION: Pseudoprogression in immunotherapy may be captured through semi-automatic software utilizing irRC or iRECIST criteria. iRECIST-based response evaluation may provide a better survival stratification compared with subjective assessment.

Fundamentals of Pharmacokinetics to Assess the Correlation Between Plasma Drug Concentrations and Different Blood Sampling Methods.

PURPOSE: Various blood collection methods were developed and used in the pharmacokinetic evaluation of drugs. However, the influence of different blood sampling methods on plasma drug concentrations has not been clarified. In the present study, we aimed to determine whether the plasma concentration of a target drug changes based on the collection site and elucidate the mechanism responsible for this change. METHODS: We compared three blood sampling methods commonly used in small animals. Eight clinical drugs were selected and administered to rats simultaneously via intracardiac injection or oral gavage. Blood samples were collected from different sites at the same individual, and pharmacokinetic properties of the drugs were then evaluated. RESULTS: Study results showed that the maximum plasma concentration or area under the curve of three study drugs was significantly higher in rats when blood was sampled from the carotid artery than when it was sampled from the caudal vein or by tail snip. CONCLUSIONS: Pharmacokinetics of certain drugs may differ based on the blood sampling site. The acid-base properties of drugs may influence pharmacokinetic evaluation. The rate and extent of drug distribution may also cause such differences and have significant effects on plasma drug levels.

Commonly used excipients modulate UDP-glucuronosyltransferase 2b7 activity to improve nalbuphine oral bioavailability in humans.

PURPOSE: Nalbuphine (NAL) is a potent opioid analgesic, but can only be administered by injection. The major aim of this study was to develop an oral NAL formulation employing known excipients as UDP-glucuronosyltransferase 2B7 (UGT2B7) inhibitors to improve its oral bioavailability. METHODS: Twenty commonly used pharmaceutical excipients were screened in vitro by using liver microsomes to identify inhibitors of UGT2B7, the major NAL metabolic enzyme. Tween 20 and PEG 400 were potent UGT2B7 inhibitors and both were co-administered (Tween-PEG) with NAL to rats and humans for pharmacokinetic and/or pharmacodynamic analyses. RESULTS: In animal studies, oral Tween-PEG (4 mg/kg of each) significantly increased the area under the plasma NAL concentration-time curve (AUC) and the maximal plasma concentration (Cmax) by 4- and 5-fold, respectively. The results of the pharmacodynamic analysis were in agreement with those of the pharmacokinetic analysis, and showed that Tween-PEG significantly enhanced the analgesic effects of orally administered NAL. In humans, oral Tween-PEG (240 mg of each) also increased NAL Cmax 2.5-fold, and AUC by 1.6-fold. CONCLUSIONS: Tween-PEG successfully improved oral NAL bioavailability and could formulate a useful oral dosage form for patient's convenience.

Simultaneous determination of nalbuphine and its prodrug sebacoly dinalbuphine ester in human plasma by ultra-performance liquid chromatography-tandem mass spectrometry and its application to pharmacokinetic study in humans.

A rapid, simple, sensitive and selective ultraperformance liquid chromatography-tandem spectrometry (UPLC-MS/MS) method for the determination of nalbuphine and its prodrug sebacoly dinalbuphine ester (SDE) was developed and validated in human plasma. The sample pretreatment involves basification and iterative liquid-liquid extraction with ethyl-ether-dichloromethane (7:3, v/v) solution, followed by LC separation and positive electrospray ionization (ESI) API-3000 mass spectrometry detection. The chromatography was on a Waters Acquity UPLC BEH HILIC column (2.1 × 100 mm, 1.7 µm). The mobile phase was composed of acetonitrile and water (83:17, v/v) that contained 0.2% formic acid and 4 mm ammonium formate at a flow rate of 0.25 mL/min. Ethylmorphine and naloxine were selected as the SDE and nalbuphine internal standard (IS), respectively. The calibration curve for both was linear over the range from 0.05 to 20 ng/mL, with correlation coefficients ≥0.995. The lower limit of quantification was set at 0.05 ng/mL. The intra- and inter-day precision values for nalbuphine and SDE were acceptable as per FDA guidelines. The method was applied successfully to determine nalbuphine concentration in human plasma samples obtained from four Taiwanese volunteers receiving intramuscularly administration of sebacoyl dinalbuphine ester. The method is sensitive, selective and directly applicable to human pharmacokinetic studies involving nalbuphine.

Blepharoptosis in infantile onset Pompe disease: Histological findings and surgical outcomes.

This retrospective observational case series is to evaluate the histopathological findings of drooping eyelids in patients with infantile-onset Pompe disease and assess the feasibility of levator muscle resection combined with conjoint fascial sheath suspension for ptosis correction. It included six patients from a single tertiary referral center with ptosis and infantile-onset Pompe disease between January 1, 2013, and December 31, 2021. They most suffered from recurrent ptosis after initial surgical correction (6/11 eyes, 54.55%). The recurrence rate was high in eyes with levator muscle resection alone (4/6 eyes, 66.67%). No recurrence of ptosis was observed in eyes with levator muscle resection combined with conjoint fascial sheath suspension. The follow-up period was approximately 16-94 months. Histopathological examination revealed that the levator muscle had the most abundant glycogen accumulation-related vacuolar changes, followed by Müller's muscle and extraocular muscles. No vacuolar changes were observed in the conjoint fascial sheath. For patients with infantile-onset Pompe disease-related ptosis, performing levator muscle resection alone is not sufficient, while utilizing conjoint fascial sheath suspension can achieve the desired long-term outcomes with minimal recurrence. These findings may have important implications for the management of ophthalmic complications in patients with infantile-onset Pompe disease.

The Association of Intravitreal Injections of Different Anti-Vascular Endothelial Growth Factor with Systemic Outcomes in Diabetic Patients.

This retrospective cohort study aimed to assess the systemic effects of three commonly available anti-vascular endothelial growth factor intravitreal injections in patients with diabetes, using data taken from a multi-institutional database in Taiwan. Patient data were sourced from the multi-institutional Chang Gung Research Database. Participants were divided into groups based on treatment with bevacizumab, ranibizumab, or aflibercept. Baseline characteristics were matched among the groups by the inverse probability of treatment weighting. The incidence rate of outcome events was calculated as the number of events divided by 100 person-years of follow-up. The cumulative incidence function was used to estimate the incidence rate of the outcome events among groups. The incidence of ischemic stroke was higher in the ranibizumab group than the bevacizumab and aflibercept groups (1.65, 0.92, and 0.61 per 100 person-years, respectively). The incidence of major adverse lower-limb events was higher in the bevacizumab group (2.95), followed by ranibizumab (2.00) and aflibercept (0.74). Major bleeding was relatively higher in bevacizumab (12.1) compared to ranibizumab (4.3) and aflibercept (3.8). All-cause death was higher for both bevacizumab (3.26) and aflibercept (2.61) when compared to ranibizumab (0.55), and all-cause admission was found to be highest with bevacizumab (58.6), followed by aflibercept (30.2), and ranibizumab (27.6). The bevacizumab group demonstrated a greater decrease in glycated hemoglobin compared to the baseline level (-0.33%). However, a few differences in the clinical condition between the groups were still observed after matching. In conclusion, this study suggests that different anti-vascular endothelial growth factor agents may be associated with various and differing systemic adverse events. The differences might also be attributed to differences in patient characteristics and clinical status.

Prognostic value of interim CT-based peritumoral and intratumoral radiomics in laryngeal and hypopharyngeal cancer patients undergoing definitive radiotherapy.

BACKGROUND AND PURPOSE: We aimed to investigate the prognostic value of peritumoral and intratumoral computed tomography (CT)-based radiomics during the course of radiotherapy (RT) in patients with laryngeal and hypopharyngeal cancer (LHC). MATERIALS AND METHODS: A total of 92 eligible patients were 1:1 randomly assigned into training and validation cohorts. Pre-RT and mid-RT radiomic features were extracted from pre-treatment and interim CT. LASSO-Cox regression was used for feature selection and model construction. Time-dependent area under the receiver operating curve (AUC) analysis was applied to evaluate the models' prognostic performances. Risk stratification ability on overall survival (OS) and progression-free survival (PFS) were assessed using the Kaplan-Meier method and Cox regression. The associations between radiomics and clinical parameters as well as circulating lymphocyte counts were also evaluated. RESULTS: The mid-RT peritumoral (AUC: 0.77) and intratumoral (AUC: 0.79) radiomic models yielded better performance for predicting OS than the pre-RT intratumoral model (AUC: 0.62) in validation cohort. This was confirmed by Kaplan-Meier analysis, in which risk stratification depended on the mid-RT peritumoral (p = 0.009) and intratumoral (p = 0.003) radiomics could be improved for OS, in comparison to the pre-RT intratumoral radiomics (p = 0.199). Multivariate analysis identified mid-RT peritumoral and intratumoral radiomic models as independent prognostic factors for both OS and PFS. Mid-RT peritumoral and intratumoral radiomics were correlated with treatment-related lymphopenia. CONCLUSION: Mid-RT peritumoral and intratumoral radiomic models are promising image biomarkers that could have clinical utility for predicting OS and PFS in patients with LHC treated with RT.

Association of Intraocular Pressure and Optical Coherence Tomography Angiography Parameters in Early Glaucoma Treatment.

This prospective study aimed to explore the effect of medical intraocular pressure (IOP) reduction on structural and capillary vessel density (VD) change by optical coherence tomography (OCT) angiography in early glaucoma. Patients with newly diagnosed glaucoma and a follow-up of ≥6 months were enrolled. An ocular examination that included slit-lamp bio-microscopy, pneumatic tonometry, gonioscopy, standard automated perimetry, and OCT angiography was performed. Quantitative OCT angiography parameters were assessed using a linear mixed model that was adjusted for inter-eye correlation. The correlations between IOP changes and OCT angiography parameter changes were analyzed using Spearman's correlation test. In total, 52 eyes of 36 participants, including 33 glaucoma eyes of 17 participants and 19 healthy eyes of 19 participants served as the case and control groups, respectively. The IOP of the case group decreased from a baseline mean of 20.4 ± 0.8 mmHg to 15.7 ± 0.5 mmHg at 3 months (p < 0.001) and to 16.1 ± 0.5 mmHg at 6 months (p < 0.001). For the subgroup with an IOP reduction of >20%, the deep macula VD was negatively correlated with baseline IOP and significantly decreased at 3 months follow-up. Additionally, change in retinal nerve fiber layer (RNFL) was positively correlated with a change in IOP at 6 months. In conclusion, the deep-layer macula VD was correlated with baseline IOP and influenced by the reduction in IOP in the short term. The changes in VD revealed the vulnerability of the deep vascular complex. The OCTA parameters provide in vivo monitoring information during medical treatment for early glaucoma.

Proton beam radiotherapy combined with anti-PD1/PDL1 immune checkpoint inhibitors for advanced hepatocellular carcinoma.

Anti-Programmed cell Death protein 1 (Anti-PD1) or Programmed Death-Ligand 1 (PDL1) immune checkpoint inhibitors provide treatment options for advanced HCC patients with low response rates. Combination therapy is becoming a major issue to improve the unmet need. Proton beam radiotherapy (PBT) could effectively control the local tumor with a low-risk injury to peripheral liver parenchyma. We retrospectively reviewed the patients who have received PBT combined with anti-PD1/PDL1 to evaluate the efficacy and safety of the advanced HCC patients. This study reviewed 29 advanced HCC patients who have received PBT and anti-PD1/PDL1 during 2016 and 2019. All were Child-Pugh A and performance status 0-1. Seventeen patients (58.6%) had extrahepatic spreading. Concurrent PBT started during anti-PD1/PDL1 with a median of 96.6 grays equivalent dose. The PBT field covered all tumors in 13 (44.8%) patients under curative intent. Other patients (55.2%) received palliative PBT that covered only the principal tumors. All patients have completed the concurrent PBT protocol. The median anti-PD1/PDL1 duration was 3.9 months. After a median follow-up of 13.2 months, the rates of 1-year PBT infield tumor control, 1-year outfield tumor control, and overall response were 90.5%, 90.9%, and 61.5%, and 70.8%, 69.2%, and 43.8%, respectively for curative-intent and palliative-control PBT. Complete response was found in 4 (30.8%) curative-intent and 1 (6.3%) palliative-control patients. The median overall progression-free survival was 27.2 months for curative-intent patients and 15.9 months for palliative-control patients. The overall survival was non-reached for both groups. The ALBI grade and Child-Pugh score change at 3-month and 6-month after PBT initiation were nonsignificant. No unexpected adverse event occurred except nine patients (31.0%) had treatment-related adverse events higher than or equal to Grade 3, including 2 (6.9%) had a radiation-induced liver injury. PBT combined with anti-PD1/PDL1 was safe without unexpected adverse events. The concurrent therapy could effectively treat advanced HCC through sustained local tumor necrosis and effective systemic tumor control for the patients who received curative-intent or palliative-control PBT combined with anti-PD1/PDL1.

Maintenance tegafur-plus-uracil after adjuvant concurrent chemoradiotherapy may improve outcome for resected oral cavity squamous cell carcinoma with extranodal extension.

Objectives: To evaluate whether tegafur-uracil maintenance (UFTm) following postoperation adjuvant cisplatin-based concurrent chemoradiotherapy (CCRT) may reduce distant metastasis in patients with resected oral cavity squamous cell carcinoma (OSCC) with pathologic extranodal extension (pENE+). Methods: A retrospective comparison was conducted between two cohorts of patients with resected pENE+ OSCC who completed adjuvant CCRT between March 2015 and December 2017, including one cohort of a phase II trial using UFTm and a trial-eligible but off-protocol cohort without using UFTm (non-UFTm) after their adjuvant CCRT. The UFTm trial enrolled patients without relapse within 2 months after the end of adjuvant CCRT and administered UFT 400 mg/day for 1 year. Kaplan-Meier methods estimated the actuarial rate of distant metastasis-free (DMF), locoregional control (LRC), event-free survival (EFS), and overall survival (OS). Results: A total of 103 patients were included in this study, 64 patients in UFTm and 39 patients in non-UFTm. Severe adverse events in UFTm included grade 3 anemia (n = 1, 1.6%) and grade 3 mucositis (n = 1, 1.6%). A total of 40 (62.5%) patients completed the full course of UFTm, while the remaining terminated UFTm earlier due to disease relapse (n = 14, 21.8%), poor compliance (n = 9, 14.1%), and adverse event (n = 1, 1.6%). The median (range) follow-up time of surviving patients was 43 (22-65) months. The outcomes compared between UFTm and non-UFTm were OS (hazard ratio [HR] 0.31 [95% CI: 0.17-0.57], p < 0·001), EFS (0.45 [0.25-0.82], 0.009), LRC (0.45 [0.19-1.05], 0.067), and DMF (0.47 [0.24-0.95], 0.035). Multivariable analysis, adjusted for UFTm, Charlson comorbidity index score 1-3, site of tongue, and number of ENE+ LN ≧4, confirmed better OS (0.29 [0.16-0.54], <0.001) and EFS (0.47 [0.26-0.85], 0.012) in favor of UFTm over non-UFTm. The 2-year DM rate was 25.8% in UFTm and 44.2% in non-UFTm. For relapsed patients in UFTm vs. non-UFTm, the rate of metastasectomy for oligometastasis was 53% vs. 6%, and the OS was 21.0 (95% CI: 17.8-24.1) months vs. 11.0 (9.1-12.8) months (p < 0.001), respectively. Conclusions: UFTm may improve the dismal outcomes of the resected pENE+ OSCC. Further investigations are needed to confirm our observations.

Prospective evaluation of the comorbidity of obstructive sleep apnea in patients with glaucoma.

STUDY OBJECTIVES: This study aimed to identify prospectively the correlation between obstructive sleep apnea (OSA) severity, ocular microcirculation changes, and visual function changes in patients with glaucoma. METHODS: We prospectively enrolled patients with glaucoma who were willing to undergo overnight polysomnography. The enrolled patients were further divided into normal tension glaucoma, high-tension glaucoma, and control. Visual field progression was analyzed using sequential standard automated perimetry. Peripapillary and macular vessel density were assessed through optical coherence tomography angiography (OCT-angiography). The associations between polysomnography parameters, OCT-angiography parameters, and visual field progression were analyzed. RESULTS: A total of 22 patients with normal tension glaucoma, 30 patients with high-tension glaucoma, and 24 control patients were enrolled. Through regression analysis, glaucoma was found to be an independent predictor of moderate-to-severe OSA (P = .035); furthermore, moderate-to-severe OSA was significantly associated with visual field progression (P = .008 in the high-tension glaucoma subgroup and P = .008 in the overall glaucoma). Additionally, OSA severity was negatively correlated with the ganglion cell complex thinning rate in the normal tension glaucoma subgroup. CONCLUSIONS: Presence of glaucoma increased the risk of moderate-to-severe OSA compared with the control group. OSA severity was related to visual field deterioration in patients with glaucoma and further associated with structural progression in the normal tension glaucoma subgroup. Careful monitoring of the comorbid OSA status of patients with glaucoma is essential to prevent disease progression. CITATION: Chan Y-H, Chuang L-H, Yu C-C, et al. Prospective evaluation of the comorbidity of obstructive sleep apnea in patients with glaucoma. J Clin Sleep Med. 2022;18(1):47-56.

Circulating p16-Positive and p16-Negative Tumor Cells Serve as Independent Prognostic Indicators of Survival in Patients with Head and Neck Squamous Cell Carcinomas.

BACKGROUND: Decisions regarding the staging, prognosis, and treatment of patients with head and neck squamous cell carcinomas (HNSCCs) are made after determining their p16 expression levels and human papillomavirus (HPV) infection status. METHODS: We investigated the prognostic roles of p16-positive and p16-negative circulating tumor cells (CTCs) and their cell counts in HNSCC patients. We enrolled patients with locally advanced HNSCCs who received definitive concurrent chemoradiotherapy for final analysis. We performed CTC testing and p16 expression analysis before chemoradiotherapy. We analyzed the correlation between p16-positive and p16-negative CTCs and HPV genotyping, tissue p16 expression status, response to chemoradiotherapy, disease-free survival, and overall survival. RESULTS: Forty-one patients who fulfilled the study criteria were prospectively enrolled for final analysis. The detection rates of p16-positive (>0 cells/mL blood) and p16-negative (≥3 cells/mL blood) CTCs were 51.2% (n = 21/41) and 70.7%, respectively. The best responses of chemoradiotherapy and the p16 positivity of CTCs are independent prognostic factors of disease progression, with hazard ratios of 1.738 (95% confidence interval (CI): 1.031-2.927), 5.497 (95% CI: 1.818-16.615), and 0.176 (95% CI: 0.056-0.554), respectively. The p16 positivity of CTCs was a prognostic factor for cancer death, with a hazard ratio of 0.294 (95% CI: 0.102-0.852). CONCLUSIONS: The p16-positive and p16-negative CTCs could predict outcomes in HNSCC patients receiving definitive chemoradiotherapy. This non-invasive CTC test could help stratify the risk and prognosis before chemoradiotherapy in clinical practice and enable us to perform de-intensifying therapies.

Correlation of corneal pigmented arc with wide epithelial thickness map in orthokeratology-treated children using optical coherence tomography measurements.

PURPOSE: To determine the intensity of corneal pigmented arc in orthokeratology (ortho-k)-treated children and its correlation with wide epithelial thickness map (ETM) obtained through anterior segment optical coherent tomography (AS-OCT). METHODS: This retrospective case series reviews medical records of children who received ortho-k treatment for myopia control. Intensity of ortho-k-associated pigmented arc after wearing ortho-k lens more than 12 months and its correlation with each sector/zone of wide ETM obtained by AS-OCT was explored. Pigmented arcs were further divided into apparent and unapparent groups, and the clinical differences between groups were determined. RESULTS: This study included 57 eyes of 29 children (mean age, 11.4 years, range 9-15); after initiating ortho-k treatment, the incidence of the corneal pigmented arc was 91.2% with mean lens wear duration of 26.1 months. Intensity of pigmented arc was significantly correlated with lens wear duration, target power, baseline degree of myopia, C zone and sectors I2, I3 and IT3 on wide ETM. Comparison between apparent and unapparent groups showed the same significant results except for C zone. After adjusting for lens wear duration and target power, sector I2 has the highest association with pigmented arc severity. CONCLUSION: Children treated with ortho-k are likely to develop ortho-k-associated pigmented arcs. The new wide ETM of AS-OCT can provide important information regarding the intensity of pigmented arc in these children. This can support customized pigmented arc-free ortho-k treatment for children in the future.

Immune Checkpoint Inhibitors for Advanced Melanoma: Experience at a Single Institution in Taiwan.

Background: Immune checkpoint inhibitors (ICIs) have significantly changed the current approach to cancer treatment. Although the use of ICIs has become the standard of care for advanced melanoma, reports of ICI use among Asian populations with melanoma are limited. Therefore, we conducted this retrospective study to assess the efficacy and safety of ICI use in Taiwanese patients. Patients: Patients with histologically confirmed melanoma treated with ICIs at Linkou Chang Gung Memorial Hospital from January 2014 to July 2019 were retrospectively reviewed. Univariant and multivariant analyses were performed to identify possible prognostic factors. Results: Among 80 patients, 45 were treatment-naïve (56.3%), and 35 received prior systemic drugs other than ICIs. Regarding treatment regimens, patients were treated with ipilimumab (n = 9), nivolumab (n = 33), pembrolizumab (n = 16), or combination drugs (n = 22). Nine patients achieved either a complete (n = 2) or partial (n = 7) response and 13 patients were stable, with a resulting response rate of 11.3% and disease control rate of 27.5%. As of the last follow-up in January 2020, patients treated with combination drugs had longer median progression-free survival (PFS) of 5.6 (95% confidence interval [CI]: 1.6-9.6) months than nivolumab (2.9 months, 95% CI: 1.9-3.9 months), pembrolizumab (3.2 months, 95% CI: 2.6-3.8 months), and ipilimumab (2.6 months, 95% CI: 2.4-2.8 months; p = 0.011). No significant differences in overall survival (OS) among the four regimens (p = 0.891) were noted. In the multivariate analysis, combination treatment, disease control, and performance ≤ 1 were independent prognostic factors for PFS. Liver metastases and no disease control were independent unfavorable prognostic factors for OS. The most common factor was skin toxicity (45%), followed by endocrine toxicity (18.8%). Patients undergoing combination treatment experienced more frequent and serious adverse events than patients undergoing monotherapy. Conclusion: ICIs demonstrated efficacy and safety in Taiwanese patients with melanoma. Combination treatment showed the greatest efficacy, but this was also accompanied by greater toxicity among the four regimens. In addition, we identified important prognostic factors, such as liver metastases, performance status, and tumor response, for both PFS and OS. These findings could provide physicians with more information to justify clinical outcomes observed in Asian patients with advanced melanoma.