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BACKGROUND: Olfactory dysfunction (OD) affects many survivors of COVID-19. Prior studies have investigated the use of platelet-rich plasma (PRP) injections for OD. We describe the first randomized controlled trial investigating topical PRP for OD treatment and contribute to existing literature illustrating PRP as an emerging therapeutic. METHODS: This is a single-blinded, randomized controlled trial conducted from July 2022 to December 2023. Adult patients with OD ≥6 months secondary to COVID-19 with Brief Smell Identification Test (BSIT) scores of ≤8/12 or SCENTinel odor intensity of ≤40/100 were included. Patients were randomized to three, monthly PRP or placebo-impregnated Surgifoam treatments into bilateral olfactory clefts. The BSIT, SCENTinel, and Questionnaire of Olfactory Disorders-Negative Statements (QOD-NS) were completed monthly through month 12. RESULTS: Of 104 patients screened, 83 participated. No significant differences in age, OD duration, BSIT, SCENTinel, or QOD-NS scores were found between PRP (n = 42) and placebo (n = 41) patients at baseline. PRP patients experienced a statistically significant increase in BSIT scores from baseline at months 5â9, 11, and 12, while placebo patients did not (p < 0.05). However, total BSIT scores were similar between the two groups throughout the study. Neither the SCENTinel odor intensity scores nor the change from baseline were significantly different between the treatment groups. At month 12, PRP patients experienced minor improvement in OD-related quality-of-life compared with placebo. CONCLUSIONS: This study is the first to describe topical PRP as a safe, experimental treatment for OD in humans. PRP may impact odor identification in post-COVID-19 OD patients, although the lack of difference in total BSIT scores highlights the need for further study.
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BACKGROUND: This is the largest study in North America investigating olfactory outcomes after pituitary surgery to date. OBJECTIVE: Characterize factors associated with subjective olfactory dysfunction (OD) and worsened sinonasal quality-of-life (QOL) after endoscopic TSA. METHODS: Patients undergoing primary TSA for secreting and non-secreting pituitary adenomas between 2017 and 2021 with pre- and post-operative SNOT-22 scores were included. Subjective OD was determined by the smell/taste dysfunction question on the SNOT-22 (smell-SNOT). RESULTS: 159 patients with pre- and post-operative SNOT-22 scores were included. Average total SNOT-22 scores worsened from pre-operative (16.91 ± 16.91) to POM1 (25.15 ± 20.83, P < .001), with no difference from pre-operative (16.40 ± 15.88) to POM6 (16.27 ± 17.92, P = .936) or pre-operative (13.63 ± 13.54) to POM12 (12.60 ± 16.45, P = .651). Average smell-SNOT scores worsened from pre-operative (0.40 ± 1.27) to POM1 (2.09 ± 2.01, P < .001), and pre-operative (0.46 ± 1.29) to POM6 (1.13 ± 2.45, P = .002), with no difference from pre-operative (0.40 ± 1.07) to POM12 (0.71 ± 1.32, P = .100). Female gender had a 0.9-point (95% CI 0.1 to 1.6) P = .021, increase in smell-SNOT at POM1, resolving by POM6 (0.1 [-0.9 to 1.1], P = .800) and POM12 (0.0 [-1.0 to 0.9], P = .942). Septoplasty with tunnel approach had a 1.1 [0.2 to 2.0] out of 5-point (P = .023) increase in smell-SNOT at POM1, resolving by POM6 (0.2 [-1.1 to 1.6], P = .764) and POM12 (0.4 [-0.9 to 1.6], P = .567). Female gender had a 9.5 (4.0 to 15.1)-point (P = .001) increase in SNOT-22 scores at POM1, resolving by POM6 (3.4 [-3.0 to 9.8], P = .292) and POM12 (6.4 [-5.4 to 18.2], P = .276). Intra-operative CSF leak had an 8.6 [2.1 to 15.1]-point (P = .009) increase in SNOT-22 scores at POM1, resolving by POM6 (5.4 [-1.7 to 12.5], P = .135), and POM12 (1.1 [-12.9 to 15.1], P = .873). CONCLUSION: Changes in subjective olfaction and sinonasal QOL after TSA may be associated with gender, operative approach, and intra-operative CSF leak, resolving 6-12 months post-operatively.
Subject(s)
Endoscopy , Olfaction Disorders , Pituitary Neoplasms , Quality of Life , Humans , Male , Female , Middle Aged , Olfaction Disorders/etiology , Endoscopy/methods , Pituitary Neoplasms/surgery , Adult , Aged , Postoperative Complications/epidemiology , Adenoma/surgery , Pituitary Gland/surgeryABSTRACT
BACKGROUND: Otolaryngology patients are a high-readmission-risk group due to the complexity of surgeries, significant alterations to speech and swallowing functions, and high postoperative complications risk. METHODS: A retrospective review was performed on patients who underwent otolaryngologic surgery at a single-academic-institution between March 2019 and February 2020. RESULTS: Among 365 discharges, 21 patients had unplanned readmissions within 30 days. On univariable analysis, acute myocardial infarction, number of total comorbidities, prior chemotherapy/radiation, active smoking, airway surgery, and enteral feeding, and on multivariable analysis, prior chemotherapy/radiation and active smoking were identified as significant readmission risk factors. Readmission risk increased from 2.43% to 7.48% and 41.67% with the addition of each risk factor. CONCLUSION: Nearly 75% of the readmissions were due to potentially preventable reasons. By identifying and proactively intervening on "at risk" patients during the perioperative timeframe, complications and readmission can be reduced, thereby improving the overall quality of care delivered.
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KEY POINTS: This study examines the impact of dupilumab on medication use for chronic rhinosinusitis with nasal polyposis (CRSwNP) and asthma patients. Patients on dupilumab had a reduction in oral/inhaled/topical steroids, antibiotics, and leukotriene receptor antagonists (LTRAs). The reduction in medication use had no impact on total polyp or SNOT-22 scores.
Subject(s)
Antibodies, Monoclonal, Humanized , Asthma , Nasal Polyps , Rhinitis , Sinusitis , Humans , Nasal Polyps/drug therapy , Sinusitis/drug therapy , Rhinitis/drug therapy , Chronic Disease , Antibodies, Monoclonal, Humanized/therapeutic use , Antibodies, Monoclonal, Humanized/administration & dosage , Asthma/drug therapy , Female , Male , Middle Aged , Adult , Leukotriene Antagonists/therapeutic use , Leukotriene Antagonists/administration & dosage , Anti-Bacterial Agents/therapeutic use , Anti-Bacterial Agents/administration & dosage , Aged , RhinosinusitisABSTRACT
BACKGROUND: Post-COVID parosmia may be due to dysautonomia and sympathetic hyperresponsiveness, which can be attenuated by stellate ganglion block (SGB). This study evaluates SGB as a treatment for post-COVID olfactory dysfunction (OD). METHODS: Retrospective case series with prospective data of patients with post-COVID OD undergoing unilateral (UL) or bilateral (BL) SGB. Patients completed Brief Smell Identification Tests (BSIT) (12 points maximum) and post-procedure surveys including parosmia severity scores on a scale of 1 (absent) to 10 (severe). Scores were compared from before treatment (pre-SGB) to after first (SGB1) or second (SGB2) treatments in overall, UL, and BL cohorts. RESULTS: Forty-seven patients with post-COVID OD underwent SGB, including 23 UL and 24 BL. Twenty patients completed pre- and post-SGB BSITs (eight UL and 12 BL). Twenty-eight patients completed postprocedure surveys (11 UL and 17 BL). There were no differences in BSIT scores from pre-SGB to post-SGB1 or post-SGB2 for the overall (p = 0.098), UL (p = 0.168), or BL (p = 0.230) cohorts. Parosmia severity for the overall cohort improved from pre-SGB (8.82 ± 1.28) to post-SGB1 (6.79 ± 2.38) and post-SGB2 (5.41 ± 2.35), with significant differences from pre-SGB to post-SGB1 (p < 0.001) and pre-SGB to post-SGB2 (p < 0.001), but not post-SGB1 to post-SGB2 (p = 0.130). Number of parosmia triggers decreased for overall (p = 0.002), UL (p = 0.030) and BL (p = 0.024) cohorts. Quality of life (QOL) improved for all cohorts regarding food enjoyment, meal preparation, and socialization (p < 0.05). CONCLUSION: SGB may improve subjective parosmia and QOL for patients with post-COVID OD, however it may not affect odor identification. Further placebo-controlled studies are warranted.
Subject(s)
Autonomic Nerve Block , COVID-19 , Olfaction Disorders , Stellate Ganglion , Humans , COVID-19/complications , Male , Female , Middle Aged , Autonomic Nerve Block/methods , Retrospective Studies , Olfaction Disorders/virology , Olfaction Disorders/therapy , Aged , Adult , SARS-CoV-2 , Treatment OutcomeABSTRACT
BACKGROUND: Enhanced Recovery After Surgery (ERAS) protocols have been developed and successfully implemented for many surgical specialties, demonstrating reductions in length of stay, post-operative complications, and resource utilization. Currently, there are few documented applications of ERAS protocols in head and neck surgery. Additional description of head and neck surgery protocol design, implementation, and outcomes will help advance postoperative care. METHODS: An ERAS protocol was designed for patients undergoing glossectomy and primary or salvage laryngectomy with or without free flap reconstruction. Following successful protocol implementation, patient outcomes and perioperative metrics were retrospectively reviewed and compared between patients prior to and following the ERAS protocol. RESULTS: Global comparison of ERAS and control group did not show statistically significant differences in measured perioperative outcomes. There were no statistically significant differences between the ERAS and control groups in age, sex, BMI, surgery type, or cancer stage. The ERAS protocol was associated with reduced variability in hospital length of stay (LOS), demonstrated through tighter interquartile ranges. For patients undergoing salvage laryngectomy, the ERAS protocol was associated with a significant reduction in 30-day readmission rates. Although not statistically significant, the median length of stay in the step-down unit (ISCU) and hospital was lower for specific patient groups. CONCLUSION: The implementation and evaluation of the ERAS protocol demonstrated improvement in select patient outcomes as well as areas for process improvement. This study demonstrates the insights that arise from review of this protocol even for an institution with perceived standardized procedures for major oncologic head and neck surgeries. LEVEL OF EVIDENCE: 3 Laryngoscope, 134:732-740, 2024.
Subject(s)
Enhanced Recovery After Surgery , Plastic Surgery Procedures , Humans , Retrospective Studies , Postoperative Complications/epidemiology , Postoperative Complications/etiology , Length of StayABSTRACT
This is the first study to examine chronic rhinosinusitis (CRS) outcomes after starting immunoglobulin (Ig) replacement therapy for patients with primary (PID) and secondary immunodeficiency (SID). This is a retrospective review of patients diagnosed with CRS from 2018 to 2022 prior to initiating Ig therapy for the treatment of PID or SID. Outcomes included medication use and Sinonasal Outcome Test (SNOT-22) scores. Ten patients met the inclusion criteria. PID and SID patients had a decrease in antibiotics (PID: 9.40 to 3.20, P = .05, SID: 8.20 to 2.00, P = .04) and steroids (PID: (5.40 to 0.60; P = .06; SID: 2.20 to 0.20, P = .047) prescribed in the year after Ig compared to the year prior. Patients with SID had a decrease in mean SNOT-22 scores by 12 months after Ig (47.50 to 20.50, P = 0.03). Patients receiving Ig for PID and SID showed decreased medication use and SID patients experienced subjective improvement in CRS symptoms in year-over-year comparison.
Subject(s)
Immunologic Deficiency Syndromes , Rhinitis , Rhinosinusitis , Sinusitis , Humans , Sinusitis/complications , Sinusitis/therapy , Sinusitis/diagnosis , Immunoglobulins/therapeutic use , Immunologic Deficiency Syndromes/therapy , Immunologic Deficiency Syndromes/drug therapy , Chronic Disease , Rhinitis/complications , Rhinitis/drug therapyABSTRACT
BACKGROUND: Poor oral health has been identified as a prognostic factor potentially affecting the survival of patients with head and neck squamous cell carcinoma. However, evidence to date supporting this association has emanated from studies based on single cohorts with small-to-modest sample sizes. METHODS: Pooled analysis of 2449 head and neck squamous cell carcinoma participants from 4 studies of the International Head and Neck Cancer Epidemiology Consortium included data on periodontal disease, tooth brushing frequency, mouthwash use, numbers of natural teeth, and dental visits over the 10 years prior to diagnosis. Multivariable generalized linear regression models were used and adjusted for age, sex, race, geographic region, tumor site, tumor-node-metastasis stage, treatment modality, education, and smoking to estimate risk ratios (RR) of associations between measures of oral health and overall survival. RESULTS: Remaining natural teeth (10-19 teeth: RR = 0.81, 95% confidence interval [CI] = 0.69 to 0.95; ≥20 teeth: RR = 0.88, 95% CI = 0.78 to 0.99) and frequent dental visits (>5 visits: RR = 0.77, 95% CI = 0.66 to 0.91) were associated with better overall survival. The inverse association with natural teeth was most pronounced among patients with hypopharyngeal and/or laryngeal, and not otherwise specified head and neck squamous cell carcinoma. The association with dental visits was most pronounced among patients with oropharyngeal head and neck squamous cell carcinoma. Patient-reported gingival bleeding, tooth brushing, and report of ever use of mouthwash were not associated with overall survival. CONCLUSIONS: Good oral health as defined by maintenance of the natural dentition and frequent dental visits appears to be associated with improved overall survival among head and neck squamous cell carcinoma patients.
Subject(s)
Carcinoma, Squamous Cell , Head and Neck Neoplasms , Humans , Squamous Cell Carcinoma of Head and Neck/epidemiology , Oral Health , Mouthwashes , Carcinoma, Squamous Cell/pathology , Case-Control Studies , Head and Neck Neoplasms/epidemiologyABSTRACT
INTRODUCTION: Chronic rhinosinusitis with nasal polyposis (CRSwNP) is often treated with endoscopic sinus surgery (ESS); however, patients may require revision surgery due to recurrence. To date, no studies have compared outcomes for combined surgery and biologic therapy for CRSwNP compared with biologic therapy alone. METHODS: Retrospective case-control study of CRSwNP patients who underwent ESS while on dupilumab or mepolizumab (ESS-biologic cohort) compared with CRSwNP patients on biologic therapy (biologic-only controls). Cohorts were matched according to indication, aspirin-exacerbated respiratory disease (AERD), sinonasal outcome test-22 (SNOT-22), and total polyp scores. RESULTS: Sixteen patients underwent ESS while on biologic therapy (13 dupilumab and 3 mepolizumab). Sixteen patients were biologic-only controls. There were no significant differences between indication, baseline SNOT-22 scores, polyp scores, and AERD status between cohorts. Patients underwent surgery a median of 33 days after starting biologic therapy. After 12 months of follow-up, the total polyp score for the ESS-biologic cohort decreased from 4.73 to 0.09 compared with a decrease from 5.22 to 3.38 for the biologic-only controls (95% confidence interval [CI] of difference: -5.37 to -1.38, Cohen's d: 2.40, p = 0.005). In the ESS-dupilumab subanalysis, the ESS-dupilumab cohort had a significant reduction in polyp burden from 4.85 to 0.00 compared with 4.88 to 3.50 for the controls (95% CI of difference: -5.68 to -1.32, Cohen's d: -1.69, p = 0.009). CONCLUSION: In CRSwNP patients, combined ESS and biologic therapy results in a significant and sustained decrease in polyp burden compared with biologic therapy alone. Larger studies are warranted to further examine the impact of combined therapy.
Subject(s)
Asthma, Aspirin-Induced , Biological Products , Nasal Polyps , Rhinitis , Rhinosinusitis , Sinusitis , Humans , Retrospective Studies , Case-Control Studies , Treatment Outcome , Sinusitis/drug therapy , Sinusitis/surgery , Nasal Polyps/drug therapy , Nasal Polyps/surgery , Chronic Disease , Rhinitis/drug therapy , Rhinitis/surgeryABSTRACT
BACKGROUND: In rural states, travel burden for complex cancer care required for head and neck squamous cell carcinoma (HNSCC) may affect patient survival, but its impact is unknown. METHODS: Patients with HPV-negative HNSCC were retrospectively identified from a statewide, population-based study. Euclidian distance from the home address to the treatment center was calculated for radiation therapy, surgery, and chemotherapy. Multivariable Cox proportional hazards models were used to examine the risk of 5-year mortality with increasing travel quartiles. RESULTS: There were 936 patients with HPV-negative HNSCC with a mean age of 60. Patients traveled a median distance of 10.2, 11.1, and 10.9 miles to receive radiation therapy, surgery, and chemotherapy, respectively. Patients in the fourth distance quartile were more likely to live in a rural location (p < 0.001) and receive treatment at an academic hospital (p < 0.001). Adjusted overall survival (OS) improved proportionally to distance traveled, with improved OS remaining significant for patients who traveled the furthest for care (third and fourth quartile by distance). Relative to patients in the first quartile, patients in the fourth had a reduced risk of mortality with radiation (HR 0.59, 95% CI 0.42-0.83; p = 0.002), surgery (HR 0.47, 95% CI 0.30-0.75; p = 0.001), and chemotherapy (HR 0.56, 95% CI 0.35-0.91; p = 0.020). CONCLUSION: For patients in this population-based cohort, those traveling greater distances for treatment of HPV-negative HNSCC had improved OS. This analysis suggests that the benefits of coordinated, multidisciplinary care may outweigh the barriers of travel burden for these patients.
Subject(s)
Head and Neck Neoplasms , Papillomavirus Infections , Humans , Middle Aged , Squamous Cell Carcinoma of Head and Neck/therapy , Retrospective Studies , Papillomavirus Infections/complications , Papillomavirus Infections/therapy , Head and Neck Neoplasms/therapy , Proportional Hazards ModelsABSTRACT
OBJECTIVES: Among the transsphenoidal (TSS) approaches to pituitary tumors, the microscopic approach (MA) has historically been the predominant technique with the increasing adoption of the endoscopic approach (EA). This study investigates national trends in TSS approaches and postoperative outcomes for MA and EA through 2021. METHODS: The TriNetX database was queried for patients undergoing TSS (MA and EA) between 2010 and 2021. Data were collected on demographics, geographic distribution of surgical centers, postoperative complications, stereotactic radiosurgery (SRT), repeat surgery, and postoperative emergency department (ED) visits. RESULTS: 8644 TSS cases were queried between 2010 and 2021. MA rates were highest until 2013 when rates of EA (52%) surpassed MA (48%) and continued to increase through 2021 (81%). From 2010 to 2015 EA had higher odds of a postoperative CSF leak (OR 3.40) and diabetes insipidus (DI (OR 2.30)) versus MA (p < 0.05); from 2016 to 2021 differences were not significant. Although there was no significant difference among approaches from 2010 to 2015 for syndrome of inappropriate antidiuretic hormone (SIADH), hyponatremia, or bacterial meningitis, from 2016 to 2021 EA had lower odds of SIADH (OR 0.54) and hyponatremia (OR 0.71), and higher odds of meningitis (OR 1.79) versus MA (p < 0.05). EA had higher odds of additional surgery (either EA or MA) after initial surgery from 2010 to 2021. From 2010 to 2015 EA had lower odds of postoperative SRT compared to MA, whereas in 2016-2021 there was no statistical difference among approaches. CONCLUSION: This study demonstrates increasing EA adoption for TSS in the United States since 2013. Complication rates have overall improved for EA compared to MA, potentially as a result of improving surgeon familiarity and experience. LEVEL OF EVIDENCE: 4 Laryngoscope, 133:2135-2140, 2023.
Subject(s)
Endoscopy , Microsurgery , Pituitary Gland , Pituitary Neoplasms , Humans , Pituitary Gland/surgery , Pituitary Neoplasms/surgery , Postoperative Complications , Retrospective Studies , Treatment Outcome , Endoscopy/standards , Endoscopy/statistics & numerical data , Endoscopy/trends , Microsurgery/standards , Microsurgery/statistics & numerical data , Microsurgery/trends , Cohort Studies , Male , Female , Adult , Middle Aged , AgedSubject(s)
Health Literacy , Rhinitis , Sinusitis , Humans , Quality of Life , Sinusitis/therapy , Rhinitis/therapy , Chronic DiseaseABSTRACT
BACKGROUND: Little is known about how factors combine to influence progression of squamous cell carcinoma of the head and neck (HNSCC). We aimed to evaluate multidimensional influences of factors associated with HNSCC stage by race. METHODS: Using retrospective data, patients with similar socioeconomic status (SES), access to care (travel time/distance), and behavioral risk factors (tobacco/alcohol use and dental care) were grouped by latent class analysis. Relative frequency differences (RFD) were calculated to evaluate latent classes by stage, race, and p16 status. RESULTS: We identified three latent classes. Advanced T-stage was higher for black (RFD = +20.2%; 95% CI: -4.6 to 44.9) than white patients (RFD = +10.7%; 95% CI: 2.1-19.3) in the low-SES/high-access/high-behavioral risk class and higher for both black (RFD = +29.6%; 95% CI: 4.7-54.5) and white patients (RFD = +23.9%; 95% CI: 15.2-32.6) in the low-SES/low-access/high-behavioral risk class. CONCLUSION: Results suggest that SES, access to care, and behavioral risk factors combine to underly the association with advanced T-stage. Additionally, differences by race warrant further investigation.
Subject(s)
Head and Neck Neoplasms , Head and Neck Neoplasms/diagnosis , Head and Neck Neoplasms/epidemiology , Head and Neck Neoplasms/therapy , Health Services Accessibility , Humans , Retrospective Studies , Risk Factors , Social Class , Socioeconomic FactorsABSTRACT
OBJECTIVES: Transoral laser surgery for glottic stenosis (transverse cordotomy and anteromedial arytenoidectomy (TCAMA)) is often complicated by granulation tissue (GT) formation. GT can cause dyspnea and may require surgical removal to alleviate airway obstruction. Inhaled corticosteroids (ICS) have been shown to reduce benign vocal fold granulomas, however its use to prevent GT formation has not been described. We aimed to analyze the effect of immediate postoperative ICS on GT formation in patients undergoing transoral laser surgery for glottic stenosis. METHODS: A retrospective analysis of patients that had transoral laser surgery for glottic stenosis from 2000 to 2019 was conducted. Surgical instances were grouped into those that received postoperative ICS and those that did not. Demographics, diagnosis, comorbidities, intraoperative adjuvant therapy, and perioperative medications were collected. Differences in GT formation and need for surgical removal were compared between groups. A multivariate exact logistic regression model was performed. RESULTS: Forty-four patients were included; 16 required 2 glottic airway surgeries (60 surgical instances). Of the 23 instances where patients received immediate postoperative ICS, 0 patients developed GT; and of the 37 instances that did not receive postoperative ICS, 15 (40.5%) developed GT (P < .0001). Eight (53.3%) of these cases returned to the OR for GT removal. ICS use was solely associated with the absence of GT formation (P = .042) in the multivariate analysis. CONCLUSIONS: Immediate postoperative use of ICS seems to be a safe and effective method to prevent granulation tissue formation and subsequent surgery in patients following transoral laser airway surgery for glottic stenosis.
Subject(s)
Laser Therapy , Vocal Cord Paralysis , Constriction, Pathologic/surgery , Glottis/surgery , Granulation Tissue , Humans , Laser Therapy/methods , Retrospective Studies , Steroids , Vocal Cord Paralysis/surgeryABSTRACT
Despite years of progress, mutation detection in cancer samples continues to require significant manual review as a final step. Expert review is particularly challenging in cases where tumors are sequenced without matched normal control DNA. Attempts have been made to call somatic point mutations without a matched normal sample by removing well-known germline variants, utilizing unmatched normal controls, and constructing decision rules to classify sequencing errors and private germline variants. With budgetary constraints related to computational and sequencing costs, finding the appropriate number of controls is a crucial step to identifying somatic variants. Our approach utilizes public databases for canonical somatic variants as well as germline variants and leverages information gathered about nearby positions in the normal controls. Drawing from our cohort of targeted capture panel sequencing of tumor and normal samples with varying tumortypes and demographics, these served as a benchmark for our tumor-only variant calling pipeline to observe the relationship between our ability to correctly classify variants against a number of unmatched normals. With our benchmarked samples, approximately ten normal controls were needed to maintain 94% sensitivity, 99% specificity and 76% positive predictive value, far outperforming comparable methods. Our approach, called UNMASC, also serves as a supplement to traditional tumor with matched normal variant calling workflows and can potentially extend to other concerns arising from analyzing next generation sequencing data.
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OBJECTIVES: Patients with laryngeal squamous cell carcinoma (LSCC) often fail radiation therapy (RT), when received as monotherapy or in combination with other treatment modalities. Mechanisms for RT failure are poorly understood. We hypothesized that tumors failing RT would have increased rates of somatic mutations in genes associated with radiation resistance, particularly in genes associated with the NFE2L2 oxidative stress pathway. Using targeted exome sequencing on pretreated LSCC tumors, we retrospectively compared somatic mutation profile with clinical data and response to treatment. METHODS: Tumors were classified as either radiation-resistant (RR) or radiation-sensitive (RS). RR was defined as persistent or recurrent disease within 2 years of receiving full-dose RT. Early stage (ES) LSCC was defined as Stage I or II tumors without lymph node involvement. Eight genes associated with radiation resistance were prioritized for analysis. RT-qPCR was performed on five NFE2L2 pathway genes. RESULTS: Twenty LSCC tumors were included and classified as either RR (n = 8) or RS (n = 12). No differences in individual rates of somatic mutations by genes associated with radiation resistance were identified. Higher rates of total mutational burden (TMB) and increased alterations associated with the NFE2L2 pathway was observed in RR vs RS tumors (P < .05). In an analysis of only ES-LSCC patients (RR, n = 3 and RS, n = 3), RR tumors had increased NFE2L2 somatic pathway mutations (P = .014) and increased NQO1 mRNA expression (P = .05). CONCLUSION: Increased TMB and NFE2L2 pathway alterations were associated with radiation resistance in LSCC. NQO1 mRNA expression may serve as a biomarker for RT response in ES-LSCC.Level of Evidence: II1.
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OBJECTIVE: To estimate the relative prognostic ability of socioeconomic status (SES) compared to overall stage for HPV-negative head and neck squamous cell carcinoma (HNSCC) MATERIALS AND METHODS: Data were obtained from the Carolina Head and Neck Cancer Epidemiology Study (CHANCE). An empirical 4-category SES classification system was created. Cox proportional hazards models, survival gradients, Bayesian information criterion (BIC), and Harrell's C index were used to estimate the prognostic ability of SES compared to stage on overall survival (OS). RESULTS: The sample consisted of 1229 patients with HPV-negative HNSCC. Patients with low SES had significantly increased risk of mortality at 5â¯years compared to patients with high SES (HR 3.11, 95% CI 2.07-4.67; pâ¯<â¯0.001), and the magnitude of effect was similar to overall stage (HR 3.01, 95% CI 2.35-3.86; pâ¯<â¯0.001 for stage IV versus I). Compared to overall stage, the SES classification system had a larger total survival gradient (35.8% vs. 29.1%), similar model fit (BIC statistic of 7412 and 7388, respectively), and similar model discriminatory ability (Harrell's C index of 0.61 and 0.64, respectively). The association between low SES and OS persisted after adjusting for age, sex, race, alcohol, smoking, overall stage, tumor site, and treatment in a multivariable model (HR 2.96, 95% CI 1.92-4.56; pâ¯<â¯0.001). CONCLUSION: SES may have a similar prognostic ability to overall stage for patients with HPV-negative HNSCC. Future research is warranted to validate these findings and identify evidence-based interventions for addressing barriers to care for patients with HNSCC.
Subject(s)
Head and Neck Neoplasms , Social Class , Squamous Cell Carcinoma of Head and Neck , Bayes Theorem , Head and Neck Neoplasms/economics , Head and Neck Neoplasms/epidemiology , Humans , Neoplasm Staging , Papillomavirus Infections , Prognosis , Squamous Cell Carcinoma of Head and Neck/economics , Squamous Cell Carcinoma of Head and Neck/epidemiologyABSTRACT
BACKGROUND: Only high-risk tumors with extranodal extension (ENE) and/or positive surgical margins (PSM) benefit from adjuvant therapy (AT) with concurrent chemoradiation (CRT) compared to radiation therapy (RT) in locally advanced head and neck squamous cell carcinoma (HNSCC). Optimal treatment for intermediate-risk tumors remains controversial. We categorized patients based on their surgical pathologic risk factors and described AT treatment patterns and associated survival outcomes. METHODS: Patients were identified from CHANCE, a population-based study, and risk was classified based on surgical pathology review. High-risk patients (n = 204) required ENE and/or PSM. Intermediate-risk (n = 186) patients had pathological T3/T4 disease, perineural invasion (PNI), lymphovascular invasion (LVI), or positive lymph nodes without ENE. Low-risk patients (n = 226) had none of these features. RESULTS: We identified 616 HPV-negative HNSCC patients who received primary surgical resection with neck dissection. High-risk patients receiving AT had favorable OS (HR 0.50, p = 0.013) which was significantly improved with the addition of chemotherapy compared to RT alone (HR 0.47, p = 0.021). When stratified by node status, the survival benefit of AT in high-risk patients persisted only among those who were node-positive (HR: 0.17, p < 0.0005). On the contrary, intermediate-risk patients did not benefit from AT (HR: 1.26, p = 0.380) and the addition of chemotherapy was associated with significantly worse OS compared to RT (HR: 1.76, p = 0.046). CONCLUSION: In high-risk patients, adjuvant chemoradiotherapy improved OS compared to RT alone. The greatest benefit was in node-positive cases. In intermediate-risk patients, the addition of chemotherapy to RT increased mortality risk and therefore should only be used cautiously in these patients.
Subject(s)
Head and Neck Neoplasms/drug therapy , Head and Neck Neoplasms/radiotherapy , Squamous Cell Carcinoma of Head and Neck/drug therapy , Squamous Cell Carcinoma of Head and Neck/radiotherapy , Aged , Chemoradiotherapy, Adjuvant/methods , Combined Modality Therapy/methods , Female , Head and Neck Neoplasms/pathology , Humans , Lymph Nodes/pathology , Male , Margins of Excision , Middle Aged , Neck Dissection/methods , Neoplasm Staging/methods , Papillomavirus Infections/pathology , Radiotherapy, Adjuvant/methods , Retrospective Studies , Squamous Cell Carcinoma of Head and Neck/pathologyABSTRACT
Adenoid cystic carcinoma (ACC) is a rare salivary gland tumor, displaying aggressive behavior with frequent recurrence and metastasis. Little information exists regarding the impact of clinicopathological parameters and adjuvant radiotherapy (aRT) on ACC disease specific (DSS) and overall survival (OS). We extracted demographic, treatment, and survival information of 1439 patients with major or minor intraoral salivary gland ACC from the Surveillance, Epidemiology, and End Results (SEER) database. The associations between tumor characteristics and aRT with OS and DSS were estimated using hazard ratios (HR) and 95% confidence intervals (CI). Submandibular gland ACCs had the worst prognosis (adjusted DSS HR = 1.48; 95% CI = 0.99-2.20, compared to parotid), and this difference was more pronounced among patients with advanced-stage tumors (adjusted DSS HR = 1.93; 95% CI = 1.13-3.30). aRT was associated with increased overall survival only among stage III submandibular ACC patients (HR = 0.64; 95% CI = 0.42-0.98) and had no benefit in any other group. In conclusion, submandibular gland ACC carries a worse prognosis than other gland subsites and may benefit from aRT. The different outcomes between submandibular gland and other major or minor gland ACCs warrant further mechanistic investigation.
ABSTRACT
PURPOSE: Racial disparities for overall survival (OS) in head and neck cancer have been well described. However, the extent to which these disparities exist for HPV-associated oropharyngeal squamous cell carcinoma (OPSCC), and the contribution of demographic, clinical, and socioeconomic status (SES) variables, is unknown. MATERIALS AND METHODS: Patients were identified from the Carolina Head and Neck Cancer Epidemiology Study (CHANCE), a population-based study in North Carolina. Cox proportional hazards regression models were used to estimate hazard ratios (HR) and 95% confidence intervals (CI) for OS in black versus white patients with sequential adjustment sets. RESULTS: A total of 157 HPV-associated OPSCC patients were identified. Of these, 93% were white and 7% were black. Black patients with HPV-associated OPSCC were more likely to be younger, have an income <$20,000, live farther away from clinic where biopsy was performed, and have advanced T stage at diagnosis. Black patients had worse OS in the unadjusted analysis (HR 4.9, 95% CI 2.2-11.1, p < 0.0001). The racial disparity in OS slightly decreased when sequentially adjusting for demographic, clinical, and SES variables. However, HR for black race remained statistically elevated in the final adjustment set which controlled for age, sex, stage, smoking, alcohol use, and individual-level household income, insurance, and education level (HR 3.4, 95% CI 1.1-10.1, p = 0.028). CONCLUSION: This is the first population-based study that confirms persistence of racial disparities in HPV-associated OPSCC after controlling for demographic, clinical, and individual-level socioeconomic factors.