Pre-clinical evaluation of APrevent® VOIS for unilateral vocal fold paralysis medialization.

Objective: To evaluate the concept and efficacy of an adjustable implant (Prototype SH30: porcine implant and APrevent® VOIS: human concept) for treatment of unilateral vocal fold paralysis (UVFP) via in vivo mini-pig studies, human computed tomographic (CT) and magnetic resonance (MR) image analysis, ex-vivo aerodynamic and acoustic analysis. Methods: Feasibility testing and prototype implantation were performed using in-vivo UVFP porcine model (n = 8), followed by a dimensional finding study using CT and MR scans of larynges (n = 75) for modification of the implant prototypes. Acoustic and aerodynamic measurements were recorded on excised canine (n = 7) larynges with simulated UVFP before and after medialization with VOIS-Implant. Results: The prototype showed in the in-vivo UVFP porcine model an improved glottic closure from grade 6 incomplete closure to complete closure (n = 5), to grade 2 incomplete closure (n = 2) and grade 3 incomplete closure (n = 1). On human CT/MR scans the identification of the correct size was successful in 97.3% using the thyroid cartilage alar "distance S" as the only parameter, which is an important step towards procedure standardization and implant design. Results were confirmed with implantation in human laryngeal cadavers (n = 44). Measurements of the acoustic and aerodynamic effects after implantation showed a significant decreased phonation threshold pressure (p = .0187), phonation threshold flow (p = .0001) and phonation threshold power (p = .0046) on excised canine larynges with simulated UVFP. Percent jitter and percent shimmer decreased (p = .2976; p = .1771) but not significant. Conclusions: Based on the preclinical results four sizes, differing in medial length, implant width and expansion direction of silicone cushions, seem to be enough to satisfy laryngeal size variations. This concept is significantly effective in medializing UVFP and improving the aerodynamic and acoustic qualities of phonation as reported in a preliminary clinical outcome study with long-term implantation. Level of Evidence: N/A.

A Deep Learning Model to Predict Knee Osteoarthritis Based on Nonimage Longitudinal Medical Record.

PURPOSE: To develop deep learning model (Deep-KOA) that can predict the risk of knee osteoarthritis (KOA) within the next year by using the previous three years nonimage-based electronic medical record (EMR) data. PATIENTS AND METHODS: We randomly selected information of two million patients from the Taiwan National Health Insurance Research Database (NHIRD) from January 1, 1999 to December 31, 2013. During the study period, 132,594 patients were diagnosed with KOA, while 1,068,464 patients without KOA were chosen randomly as control. We constructed a feature matrix by using the three-year history of sequential diagnoses, drug prescriptions, age, and sex. Deep learning methods of convolutional neural network (CNN) and artificial neural network (ANN) were used together to develop a risk prediction model. We used the area under the receiver operating characteristic (AUROC), sensitivity, specificity, and precision to evaluate the performance of Deep-KOA. Then, we explored the important features using stepwise feature selection. RESULTS: This study included 132,594 KOA patients, 83,111 females (62.68%), 49,483 males (37.32%), mean age 64.2 years, and 1,068,464 non-KOA patients, 545,902 females (51.09%), 522,562 males (48.91%), mean age 51.00 years. The Deep-KOA achieved an overall AUROC, sensitivity, specificity, and precision of 0.97, 0.89, 0.93, and 0.80 respectively. The discriminative analysis of Deep-KOA showed important features from several diseases such as disorders of the eye and adnexa, acute respiratory infection, other metabolic and immunity disorders, and diseases of the musculoskeletal and connective tissue. Age and sex were not found as the most discriminative features, with AUROC of 0.9593 (-0.76% loss) and 0.9644 (-0.25% loss) respectively. Whereas medications including antacid, cough suppressant, and expectorants were identified as discriminative features. CONCLUSION: Deep-KOA was developed to predict the risk of KOA within one year earlier, which may provide clues for clinical decision support systems to target patients with high risk of KOA to get precision prevention program.

Anemia and the Risk of Cognitive Impairment: An Updated Systematic Review and Meta-Analysis.

BACKGROUND: Cognitive impairment is one of the most common, burdensome, and costly disorders in the elderly worldwide. The magnitude of the association between anemia and overall cognitive impairment (OCI) has not been established. OBJECTIVE: We aimed to update and expand previous evidence of the association between anemia and the risk of OCI. METHODS: We conducted an updated systematic review and meta-analysis. We searched electronic databases, including EMBASE, PubMed, and Web of Science for published observational studies and clinical trials between 1 January 1990 and 1 June 2020. We excluded articles that were in the form of a review, letter to editors, short reports, and studies with less than 50 participants. The Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines were followed. We estimated summary risk ratios (RRs) with random effects. RESULTS: A total of 20 studies, involving 6558 OCI patients were included. Anemia was significantly associated with an increased risk of OCI (adjusted RR (aRR) 1.39 (95% CI, 1.25-1.55; p < 0.001)). In subgroup analysis, anemia was also associated with an increased risk of all-cause dementia (adjusted RR (aRR), 1.39 (95% CI, 1.23-1.56; p < 0.001)), Alzheimer's disease [aRR, 1.59 (95% CI, 1.18-2.13; p = 0.002)], and mild cognitive impairment (aRR, 1.36 (95% CI, 1.04-1.78; p = 0.02)). CONCLUSION: This updated meta-analysis shows that patients with anemia appear to have a nearly 1.39-fold risk of developing OCI than those without anemia. The magnitude of this risk underscores the importance of improving anemia patients' health outcomes, particularly in elderly patients.

Association between Anemia and Risk of Parkinson Disease.

METHODS: We systematically searched articles on electronic databases such as PubMed, Embase, Scopus, and Google Scholar between January 1, 2000 and July 30, 2020. Articles were independently evaluated by two authors. We included observational studies (case-control and cohort) and calculated the risk ratios (RRs) for associated with anemia and PD. Heterogeneity among the studies was assessed using the Q and I 2 statistic. We utilized the random-effect model to calculate the overall RR with 95% CI. RESULTS: A total of 342 articles were identified in the initial searches, and 7 full-text articles were evaluated for eligibility. Three articles were further excluded for prespecified reasons including insufficient data and duplications, and 4 articles were included in our systematic review and meta-analysis. A random effect model meta-analysis of all 4 studies showed no increased risk of PD in patients with anemia (N = 4, RRadjusted = 1.17 (95% CI: 0.94-1.45, p = 0.15). However, heterogeneity among the studies was significant (I 2 = 92.60, p = <0.0001). The pooled relative risk of PD in female patients with anemia was higher (N = 3, RRadjusted = 1.14 (95% CI: 0.83-1.57, p = 0.40) as compared to male patients with anemia (N = 3, RRadjusted = 1.09 (95% CI: 0.83-1.42, p = 0.51). CONCLUSION: This is the first meta-analysis that shows that anemia is associated with higher risk of PD when compared with patients without anemia. However, more studies are warranted to evaluate the risk of PD among patients with anemia.

Deep Learning Classifier with Patient's Metadata of Dermoscopic Images in Malignant Melanoma Detection.

BACKGROUND: Incidence of skin cancer is one of the global burdens of malignancies that increase each year, with melanoma being the deadliest one. Imaging-based automated skin cancer detection still remains challenging owing to variability in the skin lesions and limited standard dataset availability. Recent research indicates the potential of deep convolutional neural networks (CNN) in predicting outcomes from simple as well as highly complicated images. However, its implementation requires high-class computational facility, that is not feasible in low resource and remote areas of health care. There is potential in combining image and patient's metadata, but the study is still lacking. OBJECTIVE: We want to develop malignant melanoma detection based on dermoscopic images and patient's metadata using an artificial intelligence (AI) model that will work on low-resource devices. METHODS: We used an open-access dermatology repository of International Skin Imaging Collaboration (ISIC) Archive dataset consist of 23,801 biopsy-proven dermoscopic images. We tested performance for binary classification malignant melanomas vs nonmalignant melanomas. From 1200 sample images, we split the data for training (72%), validation (18%), and testing (10%). We compared CNN with image data only (CNN model) vs CNN for image data combined with an artificial neural network (ANN) for patient's metadata (CNN+ANN model). RESULTS: The balanced accuracy for CNN+ANN model was higher (92.34%) than the CNN model (73.69%). Combination of the patient's metadata using ANN prevents the overfitting that occurs in the CNN model using dermoscopic images only. This small size (24 MB) of this model made it possible to run on a medium class computer without the need of cloud computing, suitable for deployment on devices with limited resources. CONCLUSION: The CNN+ANN model can increase the accuracy of classification in malignant melanoma detection even with limited data and is promising for development as a screening device in remote and low resources health care.

Cost-effectiveness analysis of endoscopic tympanoplasty versus microscopic tympanoplasty for chronic otitis media in Taiwan.

BACKGROUND: Health care systems and physicians need to conform to budgets and streamline resources to provide cost-effective quality care. Although endoscopic tympanoplasty (ET) has been performed for decades, no studies on the cost-effectiveness of ET and microscopic tympanoplasty (MT) for treating chronic otitis media have been published. The present study aimed to compare the cost-effectiveness of ET and MT for treating chronic otitis media. METHODS: This study was performed using a Cohort-style Markov decision-tree economic model with a 30-year time horizon. The economic perspective was that of a third-party payer (Taiwan National Health Insurance System). Two treatment strategies were compared, namely ET and MT. The primary outcome was the incremental cost per quality-adjusted life year (QALY). Probabilities were obtained from meta-analyses. Costs were obtained from the published literature and Taiwan National Health Insurance System database. Multiple sensitivity analyses were performed to account for data uncertainty. RESULTS: The reference case revealed that the total cost of ET was $NT 20,901 for 17.08 QALY per patient. By contrast, the total cost of MT was $NT 21,171 for 17.15 QALY per patient. The incremental cost effectiveness ratio for ET versus that of MT was $NT 3703 per QALY. The cost-effectiveness acceptability curve indicated that ET was comparable to MT at a willingness-to-pay threshold of larger than $NT 35,000 per QALY. CONCLUSION: This cost-effectiveness analysis indicates that ET is comparable to MT for treating chronic otitis media in Taiwan. This result provides the latest information for physicians, the government, and third-party payers to select proper clinical practice.

Short-term Subjective and Objective Outcomes of Patients Receiving Endoscopic Transcanal Myringoplasty for Repairing Tympanic Perforations.

Objective Endoscopic transcanal myringoplasty (ETM) has been an emerging technique for repairing tympanic perforations since the late 1990s. Objective outcomes (ie, graft success rates and hearing results) of patients who received ETM are well documented; however, subjective outcomes of these patients have rarely been reported. Hence, this study evaluated subjective and objective outcomes of patients who received ETM for repairing tympanic perforations. Study Design Prospective study. Setting Tertiary care university hospital. Patients and Methods Patients who underwent ETM for perforations of the tympanic membrane were included. We evaluated subjective variables of patients receiving ETM as the primary outcome and objective variables as the secondary outcome. Results In total, 91 ears that underwent ETM were included. The mean pain scale score was 0.1 (range, 0-2) on postoperative day 3. The mean duration of pain medication was 2.0 (range, 0-3) days. The mean number of days required to resume routine activities was 1.0 (range, 1-2) days. The overall graft success was determined postoperatively at 3 months in 80 of 91 ears (87.9%). Closure of the air-bone gap to within 20 dB was achieved in 79 (86.8%) ears. Conclusion In this study, patients who received ETM had mild postoperative pain and resumed routine activities early. These patients also exhibited favorable graft success rates and hearing results at 3 months postoperatively. On the basis of our results, we conclude that patients who receive ETM for the repair of tympanic perforations have favorable short-term subjective and objective outcomes.

Endoscopic transcanal myringoplasty for tympanic perforations: An outpatient minimally invasive procedure.

OBJECTIVE: Since the 1950s, microscopic myringoplasty has been the standard surgery for repairing a perforated tympanic membrane. In addition to conventional microscopic myringoplasty, endoscopic myringoplasty has been an emerging technique since the late 1990s. This study evaluated the efficacy of endoscopic transcanal myringoplasty for repairing tympanic perforations and examined the minimally invasive feature of this technique (no postauricular incision, no canalplasty). METHODS: We retrospectively reviewed the medical records of patients who underwent endoscopic transcanal myringoplasty for perforations of the tympanic membrane. The main outcome was the overall rate of graft success of endoscopic transcanal myringoplasty. RESULTS: A total of 181 patients were included in the analysis. The overall graft success was determined in 163 of 181 patients (92.8%). The mean preoperative and postoperative air-bone gaps were 19.3dB and 7.8dB, respectively, revealing a significant improvement of 11.5dB (Cohen's d, 1.27; 95% CI, 1.03-1.50; P<0.05; paired t test) in the air-bone gap. The rate of graft success with partial visualization of the perforation margin was comparable to that with complete visualization of the perforation margin. Larger sizes of perforations were significantly associated with lower rates of graft success (P<0.01). CONCLUSION: Our study revealed that the rate of graft success and hearing results of endoscopic transcanal myringoplasty and microscopic myringoplasty are comparable for repairing perforations of the tympanic membrane. Visualization of the perforation margin by otoscopy did not affect the rate of graft success. However, endoscopic transcanal myringoplasty is less invasive because this technique does not require postauricular incision, canalplasty, and general anesthesia.

Learning curve for endoscopic tympanoplasty: Initial experience of 221 procedures.

BACKGROUND: The learning curve for endoscopic tympanoplasty has never been quantitatively reported. The present study depicted the learning curve for endoscopic tympanoplasty and evaluated how many procedures an otologist requires to attain proficiency in this technique. METHODS: We reviewed the medical charts of consecutive patients who underwent endoscopic tympanoplasty between January 1, 2013 and June 1, 2015. We enrolled patients with simple perforations of the tympanic membrane and excluded those with ossicular chain disease. The main outcome was learning curves for endoscopic tympanoplasty, which illustrated changes in the mean operative time and graft success rate according to the patient numbers. We subsequently estimated and verified the threshold value using statistical methods. RESULTS: A total of 221 procedures were included. For the learning curve of the mean operative time, the time gradually decreased from 75 minutes to 55 minutes. After the 150th patient, the mean operative time stabilized to < 60 minutes. For the learning curve of the graft success rate, the rate sharply increased from 75% to 95%. After the 50th patient, the graft success rate reached a plateau and fluctuated between 85% and 100%. We subsequently verified that the 50th and 150th patients were appropriate threshold values. Moreover, the graft success rate of perforations < 50% was significantly higher than that of perforations > 50%. CONCLUSION: These curves illustrate significant progress of the surgeon during the first 50 patients, considering the graft success rate, reaching an advanced level after the 150th patient, considering the mean operating time.

Comparison of endoscopic transcanal myringoplasty and endoscopic type I tympanoplasty in repairing medium-sized tympanic perforations.

OBJECTIVE: The tympanomeatal flap elevation technique has been used in tympanoplasty for decades; however, this procedure has disadvantages. In recent years, endoscopic transcanal myringoplasty (ETM) has been increasingly practiced and has yielded positive results.This study compares the efficacy of ETM and endoscopic type I tympanoplasty (ETT) in repairing medium-sized perforations of the tympanic membrane. METHODS: This retrospective medical record review included patients undergoing surgery for medium-sized perforations of the tympanic membrane from January 1, 2013 to August 1, 2015. We divided our patients into 2 groups: the ETM group and ETT group. The main outcome measure was comparison of the graft take rates and hearing results between ETM and ETT. RESULTS: A total of 113 patients were enrolled in this study; of these patients, 64 underwent ETM and 49 received ETT. The overall graft take rates and improvement of air-bone gaps were comparable between the groups. However, the patients in the ETM group had shorter operative times and fewer follow-up visits over 3 months than those in the ETT group did. CONCLUSION: We recommend that ETM (instead of ETT) be used for repairing medium-sized perforations of the tympanic membrane.

Comparison of the efficacy of endoscopic tympanoplasty and microscopic tympanoplasty: A systematic review and meta-analysis.

OBJECTIVES: Microscopic tympanoplasty has been the standard surgery for repairing perforated tympanic membranes since the 1950s, but endoscopic tympanoplasty has been increasingly practiced since the late 1990s. In this study, we compared the efficacies of endoscopic and microscopic tympanoplasty. DATA SOURCES: PubMed, Embase, MEDLINE, and the Clinical Trial Register. REVIEW METHODS: We conducted a systematic review and meta-analysis following the Preferred Reporting Items for Systematic Reviews and Meta-Analysis statement. We included clinical studies that compared the efficacies of endoscopic and microscopic tympanoplasty. We assessed the risk of bias and calculated the pooled relative risk (RR) estimates with 95% confidence interval (CI). RESULTS: We identified four studies (involving 266 patients in total) that met the inclusion criteria. The pooled tympanic membrane closure rates and hearing results of endoscopic and microscopic tympanoplasty were comparable (85.1% vs. 86.4%, respectively; RR: 0.98; 95% CI: 0.85 to 1.11; I2 = 0) (mean difference of improvements of air-bone gaps: -2.73; 95% CI: -6.73 to 1.28; I2 = 80%). The pooled canalplasty rate of endoscopic tympanoplasty was significantly lower than that of microscopic tympanoplasty. Patients receiving endoscopic tympanoplasty had a more desirable cosmetic result than did those receiving microscopic tympanoplasty. CONCLUSIONS: Our up-to-date review evidences the comparable tympanic membrane closure rates and hearing results for endoscopic and microscopic tympanoplasty. Patients receiving endoscopic tympanoplasty have a lower canalplasty rate and more desirable cosmetic result than do those receiving microscopic tympanoplasty. Laryngoscope, 127:1890-1896, 2017.

Endoscopic Transcanal Myringoplasty for Anterior Perforations of the Tympanic Membrane.

Importance: Repairing anterior perforations of the tympanic membrane has been challenging for otolaryngologists. Therefore, devising a simple and effective technique for performing the repair is crucial. Objective: To assess the results of endoscopic transcanal myringoplasty for repairing anterior perforations of the tympanic membrane. Design, Setting, and Participants: This medical record review included 59 patients who underwent endoscopic transcanal myringoplasty from January 1, 2013, to June 1, 2015, at PoJen General Hospital, Taipei, Taiwan. Patients with ossicular chain disease and cholesteatoma or inadequate follow-up were excluded. Patients were followed up for 6 months, and final follow-up was completed on January 1, 2016. Main Outcomes and Measures: The main outcome was the rate of overall graft success after endoscopic transcanal myringoplasty. Secondary outcomes included hearing results and prognostic factors. Results: The study sample included the medical records of 59 patients (30 men [51%]; 29 women [49%]; mean [SD] age, 49.5 [13.1] years) who underwent endoscopic transcanal myringoplasty. Overall, 55 patients (93%) had a successful graft at 6 postoperative months. The mean (SD) preoperative and postoperative air-bone gaps were 15.9 (9.4) and 5.4 (7.0) dB, respectively, revealing a significant mean (SD) improvement of 10.3 (7.6) dB (Cohen d, 1.27; 95% CI, 0.90-1.63; P < .001, paired t test) in the gap. The postoperative air-bone gap in 46 patients (78%) was less than 10 dB; in 12 patients (20%), 10 to 20 dB; and in 1 patient (2%), more than 20 dB. Postoperative otorrhea significantly affected the graft success rate (odds ratio, 52.00; 95% CI, 4.08-662.55; P < .01, χ2 test). The visualization of the perforation margin (complete or partial) was not significantly associated with the graft success rate. However, partial visualization of the perforation margin significantly prolonged the mean (SD) operative time (complete vs partial, 59.2 [13.7] vs 68.1 [14.1] minutes; Cohen d, 0.64; 95% CI, 0.12-1.18; P = .02, t test). Conclusions and Relevance: The rate of graft success and hearing outcomes for endoscopic transcanal myringoplasty are comparable with those of microscopic myringoplasty for repairing anterior perforations of the tympanic membrane. However, the present technique is simpler because postauricular incision, canalplasty, and general anesthesia are not required. Thus, endoscopic transcanal myringoplasty should be considered for repairing anterior perforations of the tympanic membrane.

Nasal dissemination of a single-clone IgH-rearranged conjunctival MALT lymphoma through the nasolacrimal duct: A case report.

The aim of the present study was to report a rare case of single-clone, immunoglobulin heavy chain (IgH)-rearranged mucosa-associated lymphoid tissue (MALT) lymphoma in the conjunctiva, with nasal cavity dissemination through the nasolacrimal duct. A 24-year-old female was diagnosed with MALT lymphoma of the nasal cavity at the Department of Otolaryngology, Wan Fang Medical Center, Taipei Medical University (Tapei, Taiwan) in October 2008. A biopsy of the relapsing conjunctival lesion revealed a MALT lymphoma by pathological staining, while a single-clone, IgH-rearranged tumor lesion in the nasal cavity and conjunctiva was confirmed using continuous sinus computed tomography scans and polymerase chain reaction. Tumor lesions were negative for Helicobacter pylori and Chlamydia infection, but exhibited bilateral neck lymph node dissemination. A combination of radiation therapy (a total dosage of 46.8 Gray, in two phases covering the left lacrimal sac, nasal cavity and bilateral neck region) and topical ciprofloxacin plus steroid (0.3% ciprofloxacin 4 times a day and betamethasone eye ointment before sleep for 1 month) was provided as an effective therapeutic strategy, and no recurrence was found in the next 3 years. The nasolacrimal duct serves as a channel for conjunctival tumor spreading and is easily neglected. IgH-involved translocation in MALT lymphoma is a factor in the progression of the disease, and aggressive combination therapy is essential for a high-risk, disseminated IgH-rearranged MALT lymphoma.

Curative-Intent Aggressive Treatment Improves Survival in Elderly Patients With Locally Advanced Head and Neck Squamous Cell Carcinoma and High Comorbidity Index.

For locally advanced head and neck squamous cell carcinoma (HNSCC), therapeutic decisions depend on comorbidity or age. We estimated the treatment outcomes of patients with different Charlson comorbidity index (CCI) scores and ages to determine whether aggressive treatment improves survival.Data from the Taiwan National Health Insurance and cancer registry databases were analyzed, and we included >20-year-old patients with American Joint Committee on Cancer (AJCC) stage III or IV HNSCC (International Classification of Diseases, Ninth Revision, Clinical Modification codes 140.0-148.9) undergoing surgery, chemotherapy (CT), radiotherapy (RT), concurrent chemoradiotherapy (CCRT), sequential CT and RT, or surgery with adjuvant treatment. The exclusion criteria were a past cancer history, distant metastasis, AJCC stage I or II, missing sex data, an age < 20 years, nasopharyngeal cancer, in situ carcinoma, sarcoma, and HNSCC recurrence. The index date was the date of first HNSCC diagnosis, and comorbidities were scored using the CCI. The enrolled patients were categorized into Group 1 (curative-intent aggressive treatments) and Group 2 (best supportive care or palliative treatments).We enrolled 21,174 stage III or IV HNSCC patients without distant metastasis (median follow-up, 3.25 years). Groups 1 and 2 comprised 18,584 and 2232 patients, respectively. After adjustment for age, sex, and clinical stage, adjusted hazard ratios (95% confidence intervals) of overall death in Group 1 were 0.33 (0.31-0.35), 0.34 (0.31-0.36), and 0.37 (0.28-0.49), and those of all-cause death among patients undergoing curative surgical aggressive treatments were 1.13 (0.82-1.55), 0.67 (0.62-0.73), and 0.49 (0.46-0.53) for CCI scores of ≥10, 5 to 9, and <5, respectively.Aggressive treatments improve survival in elderly (≥65 years) and critically ill HNSCC patients. Curative nonsurgical aggressive treatments including definitive RT or CCRT might be suitable for HNSCC patients with CCI scores ≥10.

Outcomes of Induction Chemotherapy for Head and Neck Cancer Patients: A Combined Study of Two National Cohorts in Taiwan.

The use of induction chemotherapy (CT) is controversial. We compared the survival of head and neck cancer patients receiving docetaxel- or platinum-based induction CT before concomitant chemoradiotherapy (CCRT) with the survival of those receiving upfront CCRT alone. Data from the National Health Insurance and cancer registry databases in Taiwan were linked and analyzed. We enrolled patients who had head and neck cancer between January 1, 2002 and December 31, 2011. Follow-up was from the index date to December 31, 2013. We included head and neck patients diagnosed according to the International Classification of Diseases, Ninth Revision, Clinical Modification codes 140.0-148.9 who were aged >20 years, at American Joint Committee on Cancer clinical cancer stage III or IV, and receiving induction CT or platinum-based CCRT. The exclusion criteria were a cancer history before head and neck cancer diagnosis, distant metastasis, AJCC clinical cancer stage I or II, receipt of platinum and docetaxel before radiotherapy, an age <20 years, missing sex data, docetaxel use during or after RT, induction CT for >8 weeks before RT, induction CT alone before RT, cetuximab use, adjuvant CT within 90 days after RT completion, an RT dose <7000 cGy, curative head and neck cancer surgery before RT, nasopharyngeal cancer, in situ carcinoma, sarcoma, and head and neck cancer recurrence. We enrolled 10,721 stage III-IV head and neck cancer patients, with a median follow-up of 4.18 years (interquartile range, 3.25 years). The CCRT (arm 1), docetaxel-based induction CT (arm 2), and platinum-based CCRT (arm 3; control arm) groups comprised 7968, 503, and 2232 patients, respectively. Arm 3 was used to investigate mortality risk after induction CT. After adjustment for age, sex, clinical stage, and comorbidities, the adjusted hazard ratios (aHRs) (95% confidence interval [CI]) for overall death were 1.37 (1.22-1.53) and 1.44 (1.36-1.52) in arms 2 and 3, respectively. In a disease-specific survival rate analysis, aHRs (95% CI) of head and neck cancer-related death were 1.29 (1.14-1.46) and 1.47 (1.38-1.56) in arms 2 and 3, respectively. Compared with CCRT alone, docetaxal- or platinum-based induction CT did not improve survival but increased the risk of all-cause and head and neck cancer-related death.

Dementia Risk in Irradiated Patients With Head and Neck Cancer.

Patients with head and neck cancer are treated through surgery, radiotherapy (RT), and chemotherapy (CT). Carotid artery damage and neurotoxicity were previously observed in these patients. This study estimated the dementia risk associated with different treatment modalities in a head and neck cancer population with long-term follow-up. Taiwan's National Health Insurance claims database and a cancer registry database from the Collaboration Center of Health Information Application were linked for the present analysis. Patients with head and neck cancer, treated from January 1, 2002 to December 31, 2010, were included in the study. The follow-up duration was the period from the index date to December 31, 2012. Inclusion criteria were head and neck cancer; an age >20 years; and having undergone surgery, CT, concurrent CT, or surgery with adjuvant treatment. Exclusion criteria were another cancer diagnosed before the head and neck cancer, death or being diagnosed with dementia within 2 years after the treatment of the head and neck cancer, stroke before the index date, distant metastasis, in situ carcinoma, sarcoma, head and neck cancer recurrence, an unknown sex, and an age <20 years. In total, 20,135 patients were included. In patient groups that underwent surgery alone, surgery and adjuvant chemoradiotherapy, and chemoradiotherapy alone, the dementia incidence per 1000 person-years was 1.44, 1.04, and 1.98, respectively. The crude hazard ratio (HR) of dementia was 1.84 (95% confidence interval [CI] 1.21-2.81) in the RT with or without CT group. After adjustment for age, sex, clinical stage, and comorbidity, the HR was 1.92 (95% CI 1.14-3.24). Examining the dementia risk in patients who received different treatment modalities according to the Cox proportional-hazard model revealed that an age >65 years and having undergone RT with or without CT were risk factors (P < 0.001 and P = 0.015; and HRs of 16.5 and 1.92, respectively). The dementia risk in patients at different clinical stages was not significantly different among the various treatment groups, regardless of whether the patients received RT. However, younger (<65 y) patients who received RT with or without CT had a 2.96-fold (95% CI 1.24-7.08) higher risk of dementia and a 3.54-fold (95% CI 1.32-9.51) higher adjusted HR compared with the surgery-alone group. Patients who received a total radiation dose >6660 cGy exhibited a 1.69-fold (95% CI 0.97-2.95, P = 0.063) higher dementia risk compared with those who received a total radiation dose <6660 cGy. Receiving a higher radiation dose increased the dementia risk and persistently escalated the dementia incidence even 9 years after RT. Younger (<65 y) patients have a high risk of dementia after RT. The selection of young patients for dose de-escalation requires improvement for reducing irradiation to the neck and areas near brain tissues, particularly in Taiwan, where the median patient age is 53 years.