Assessing Quality of Life among Radiation-Induced Hypopituitary Patients.

Introduction Radiation-induced hypopituitarism (RIH) has long been recognized as one of the deleterious side effects of skull base radiation. This study aims to assess the quality of life (QoL) among patients with RIH compared with radiated patients who did not develop hypopituitarism using the validated Anterior Skull Base Questionnaire (ASBQ). Methods This was a single-institution retrospective cohort study. Included patients had a history of anterior skull base tumor, underwent at least one round of radiation to the skull base, and had filled out at least one ASBQ survey after their radiation treatment. Three statistical models were used to determine the effect of hypopituitarism and treatment on QoL scores. Results A total of 145 patients met inclusion criteria, and 330 ASBQ surveys were analyzed. Thirty-five percent (51/145) had evidence of RIH at some point after their radiation treatment. Those with hypopituitarism had significantly lower overall ASBQ scores across all three models even after adjusting for potential confounders and intraperson correlation (average decrease of 0.24-0.45 on a 5-point Likert scale; p -values ranging from 0.0004 to 0.018). The increase in QoL with hormonal replacement was modulated by time out from radiation, with long-term survivors (5+ years out from radiation) gaining the most benefit from treatment (increase of 0.89 on a 5-point Likert scale, p 0.0412), especially in the vitality domain. Conclusion This data demonstrates that hypopituitarism is an independent predictor of lower QoL. Early detection and appropriate treatment are essential to avoid the negative impact of hypopituitarism on QoL.

Comparing Individualized Survival Predictions From Random Survival Forests and Multistate Models in the Presence of Missing Data: A Case Study of Patients With Oropharyngeal Cancer.

Background: In recent years, interest in prognostic calculators for predicting patient health outcomes has grown with the popularity of personalized medicine. These calculators, which can inform treatment decisions, employ many different methods, each of which has advantages and disadvantages. Methods: We present a comparison of a multistate model (MSM) and a random survival forest (RSF) through a case study of prognostic predictions for patients with oropharyngeal squamous cell carcinoma. The MSM is highly structured and takes into account some aspects of the clinical context and knowledge about oropharyngeal cancer, while the RSF can be thought of as a black-box non-parametric approach. Key in this comparison are the high rate of missing values within these data and the different approaches used by the MSM and RSF to handle missingness. Results: We compare the accuracy (discrimination and calibration) of survival probabilities predicted by both approaches and use simulation studies to better understand how predictive accuracy is influenced by the approach to (1) handling missing data and (2) modeling structural/disease progression information present in the data. We conclude that both approaches have similar predictive accuracy, with a slight advantage going to the MSM. Conclusions: Although the MSM shows slightly better predictive ability than the RSF, consideration of other differences are key when selecting the best approach for addressing a specific research question. These key differences include the methods' ability to incorporate domain knowledge, and their ability to handle missing data as well as their interpretability, and ease of implementation. Ultimately, selecting the statistical method that has the most potential to aid in clinical decisions requires thoughtful consideration of the specific goals.

Increased Nerve Density Adversely Affects Outcome in Oral Cancer.

PURPOSE: Perineural invasion (PNI) in oral cavity squamous cell carcinoma (OSCC) is associated with poor survival. Because of the risk of recurrence, patients with PNI receive additional therapies after surgical resection. Mechanistic studies have shown that nerves in the tumor microenvironment promote aggressive tumor growth. Therefore, in this study, we evaluated whether nerve density (ND) influences tumor growth and patient survival. Moreover, we assessed the reliability of artificial intelligence (AI) in evaluating ND. EXPERIMENTAL DESIGN: To investigate whether increased ND in OSCC influences patient outcome, we performed survival analyses. Tissue sections of OSCC from 142 patients were stained with hematoxylin and eosin and IHC stains to detect nerves and tumor. ND within the tumor bulk and in the adjacent 2 mm was quantified; normalized ND (NND; bulk ND/adjacent ND) was calculated. The impact of ND on tumor growth was evaluated in chick chorioallantoic-dorsal root ganglia (CAM-DRG) and murine surgical denervation models. Cancer cells were grafted and tumor size quantified. Automated nerve detection, applying the Halo AI platform, was compared with manual assessment. RESULTS: Disease-specific survival decreased with higher intratumoral ND and NND in tongue SCC. Moreover, NND was associated with worst pattern-of-invasion and PNI. Increasing the number of DRG, in the CAM-DRG model, increased tumor size. Reduction of ND by denervation in a murine model decreased tumor growth. Automated and manual detection of nerves showed high concordance, with an F1 score of 0.977. CONCLUSIONS: High ND enhances tumor growth, and NND is an important prognostic factor that could influence treatment selection for aggressive OSCC. See related commentary by Hondermarck and Jiang, p. 2342.

Prognostic value of CD103+ tumor-infiltrating lymphocytes and programmed death ligand-1 (PD-L1) combined positive score in recurrent laryngeal squamous cell carcinoma.

OBJECTIVES: In an evolving era of immunotherapeutic options for persistent or recurrent laryngeal squamous cell carcinoma (LSCC), there is a need for improved biomarkers of treatment response and survival to inform optimal treatment selection and prognostication. Herein, our primary objective was to explore correlations between tumor infiltrating lymphocytes (TILs) and PD-L1 Combined Positive Score (CPS). Secondarily, we sought to explore their combined association with survival outcomes in patients with persistent or recurrent LSCC treated with salvage surgery. MATERIALS AND METHODS: This was a retrospective cohort study at a single academic medical center. Immunohistochemistry staining for TILs and PD-L1 was performed on a tissue microarray of persistent or recurrent LSCC pathologic specimens. Correlations between TIL subsets and PD-L1 CPS were examined using Pearson's correlation coefficient and survival outcomes were analyzed with the Kaplan-Meier method and log-rank tests. RESULTS: Only CD103+ TILs showed a statistically significant, weakly-positive correlation with PD-L1 CPS (r2 = 0.264, p < 0.015). No other TIL subsets correlated with PD-L1 CPS in our cohort. The most favorable survival outcomes were seen in patients with pathologic N0 tumors showing high CD103+ TILs and/or high PD-L1 CPS staining. CONCLUSION: Among patients with persistent or recurrent LSCC, CD103+ TILs only modestly correlated with PD-L1 CPS. A combined biomarker score incorporating CD103+ TILs and PD-L1 CPS greatly enhanced survival discrimination. This model may have additional utility in predicting the clinical benefit of immunotherapies in persistent or recurrent LSCC in the future.

Surgical Management of Rhabdomyosarcoma of the Nasal Cavity and Paranasal Sinuses: Analysis of Operative Indications, Settings, and Outcomes.

Objectives The role of surgery in management of sinonasal rhabdomyosarcoma (SNRMS) has traditionally been limited, owing to anatomic and technological challenges and the established role of systemic therapy. Herein, we report our institutional experience with surgical management of SNRMS, with a particular focus on operative approaches, extent and outcomes. Design This study is a retrospective cohort study. Setting This study was conducted at a single-institution, academic center. Participants Patients of any age with histologically confirmed RMS of the nasal cavity, maxillary, ethmoid, frontal, or sphenoid sinus, nasolacrimal duct, or nasopharynx presenting between 1994 and 2020 were included in this study. Main Outcome Measures Demographics, tumor characteristics, operative settings, complications and recurrence, and survival outcomes were the primary outcomes of this study. Results Our study cohort comprised of 29 patients (mean [range] age: 27.0 [3.1-65.7], n = 12 [41%] female). Tumors of the nasal cavity ( n = 10, 35%) and ethmoid sinuses ( n = 10, 35%) and those with alveolar histology ( n = 21, 72%) predominated. Patients who had surgery as part of their treatment ( n = 13, 45%) had improved distant metastasis-free survival (DMFS) overall (hazard ratio [HR]: 0.32, 95% CI: 0.11, 0.98, p = 0 .05 ) as compared with those who did not have surgery. Surgical approaches included open ( n = 7), endoscopic ( n = 4), and combined ( n = 2). Eight of these 13 patients (62%) had an R0 resection. Additionally, surgical salvage of recurrent disease was employed in five patients (17%). Conclusion SNRMS is an aggressive malignancy with a high rate of recurrence and spread requiring a multidisciplinary approach for optimal outcomes. Our data supports an expanding role for surgery for SNRMS given its feasibility, tolerability, and potential to improve outcomes.

Spatial and Transcriptomic Analysis of Perineural Invasion in Oral Cancer.

PURPOSE: Perineural invasion (PNI), a common occurrence in oral squamous cell carcinomas, is associated with poor survival. Consequently, these tumors are treated aggressively. However, diagnostic criteria of PNI vary and its role as an independent predictor of prognosis has not been established. To address these knowledge gaps, we investigated spatial and transcriptomic profiles of PNI-positive and PNI-negative nerves. EXPERIMENTAL DESIGN: Tissue sections from 142 patients were stained with S100 and cytokeratin antibodies. Nerves were identified in two distinct areas: tumor bulk and margin. Nerve diameter and nerve-to-tumor distance were assessed; survival analyses were performed. Spatial transcriptomic analysis of nerves at varying distances from tumor was performed with NanoString GeoMx Digital Spatial Profiler Transcriptomic Atlas. RESULTS: PNI is an independent predictor of poor prognosis among patients with metastasis-free lymph nodes. Patients with close nerve-tumor distance have poor outcomes even if diagnosed as PNI negative using current criteria. Patients with large nerve(s) in the tumor bulk survive poorly, suggesting that even PNI-negative nerves facilitate tumor progression. Diagnostic criteria were supported by spatial transcriptomic analyses of >18,000 genes; nerves in proximity to cancer exhibit stress and growth response changes that diminish with increasing nerve-tumor distance. These findings were validated in vitro and in human tissue. CONCLUSIONS: This is the first study in human cancer with high-throughput gene expression analysis in nerves with striking correlations between transcriptomic profile and clinical outcomes. Our work illuminates nerve-cancer interactions suggesting that cancer-induced injury modulates neuritogenesis, and supports reclassification of PNI based on nerve-tumor distance rather than current subjective criteria.

Impact of Nodal Metastases in HPV-Negative Oropharyngeal Cancer.

BACKGROUND: The updated American Joint Committee on Cancer (AJCC) 8th Edition staging manual restructured nodal classification and staging by placing less prognostic emphasis on nodal metastases for human papillomavirus (HPV)-positive oropharyngeal squamous cell carcinoma (OPSCC). However, there was no change for HPV-negative OPSCC. The purpose of our study is to examine the impact of nodal metastases on survival in HPV-negative OPSCC. METHODS: HPV-negative OPSCC was queried from the National Cancer Database (NCDB) and Surveillance, Epidemiology and End Results program (SEER) databases. Univariable and multivariable models were utilized to determine the impact of nodal status on overall survival. These patients were reclassified according to AJCC 8 HPV-positive criteria (TNM8+) and risk stratification was quantified with C-statistic. RESULTS: There were 11,147 cases of HPV-negative OPSCC in the NCDB and 3,613 cases in SEER that were included in the nodal classification analysis. Unlike nonoropharyngeal malignancies, increased nodal stage is not clearly associated with survival for patients with OPSCC independent of HPV status. When the TNM8+ was applied to HPV-negative patients, there was improved concordance in the NCDB cohort, 0.561 (plus minus) 0.004 to 0.624 (plus minus) 0.004 (difference +0.063) and the SEER cohort, 0.561 (plus minus) 0.008 to 0.625 (plus minus) 0.008 (difference +0.065). CONCLUSIONS: We demonstrated a reduced impact of nodal metastasis on OPSCC survival, independent of HPV status and specific to OPSCC. IMPACT: We demonstrate, for the first time that when nodal staging is deemphasized as a part of overall staging, we see improved concordance and risk stratification for HPV-negative OPSCC. The exact mechanism of this differential impact remains unknown but offers a novel area of study.

Development and Assessment of a Model for Predicting Individualized Outcomes in Patients With Oropharyngeal Cancer.

Importance: Recent insights into the biologic characteristics and treatment of oropharyngeal cancer may help inform improvements in prognostic modeling. A bayesian multistate model incorporates sophisticated statistical techniques to provide individualized predictions of survival and recurrence outcomes for patients with newly diagnosed oropharyngeal cancer. Objective: To develop a model for individualized survival, locoregional recurrence, and distant metastasis prognostication for patients with newly diagnosed oropharyngeal cancer, incorporating clinical, oncologic, and imaging data. Design, Setting, and Participants: In this prognostic study, a data set was used comprising 840 patients with newly diagnosed oropharyngeal cancer treated at a National Cancer Institute-designated center between January 2003 and August 2016; analysis was performed between January 2019 and June 2020. Using these data, a bayesian multistate model was developed that can be used to obtain individualized predictions. The prognostic performance of the model was validated using data from 447 patients treated for oropharyngeal cancer at Erasmus Medical Center in the Netherlands. Exposures: Clinical/oncologic factors and imaging biomarkers collected at or before initiation of first-line therapy. Main Outcomes and Measures: Overall survival, locoregional recurrence, and distant metastasis after first-line cancer treatment. Results: Of the 840 patients included in the National Cancer Institute-designated center, 715 (85.1%) were men and 268 (31.9%) were current smokers. The Erasmus Medical Center cohort comprised 300 (67.1%) men, with 350 (78.3%) current smokers. Model predictions for 5-year overall survival demonstrated good discrimination, with area under the curve values of 0.81 for the model with and 0.78 for the model without imaging variables. Application of the model without imaging data in the independent Dutch validation cohort resulted in an area under the curve of 0.75. This model possesses good calibration and stratifies patients well in terms of likely outcomes among many competing events. Conclusions and Relevance: In this prognostic study, a multistate model of oropharyngeal cancer incorporating imaging biomarkers appeared to estimate and discriminate locoregional recurrence from distant metastases. Providing personalized predictions of multiple outcomes increases the information available for patients and clinicians. The web-based application designed in this study may serve as a useful tool for generating predictions and visualizing likely outcomes for a specific patient.

Understanding the impact of high-risk human papillomavirus on oropharyngeal squamous cell carcinomas in Taiwan: A retrospective cohort study.

BACKGROUND AND OBJECTIVES: Human papillomavirus (HPV)-driven oropharyngeal squamous cell carcinoma (OPSCC) is increasing globally. In Taiwan, HPV-positive OPSCC is obscured by tobacco, alcohol, and betel quid use. We investigated the role of high-risk HPV (hrHPV) in a large retrospective Taiwan OPSCC cohort. METHODS AND RESULTS: The cohort of 541 OPSCCs treated at Chang Gung Memorial Hospital from 1998-2016 consisted of 507 men (94%) and 34 women (6%). Most used tobacco (81%), alcohol (51%), and betel quid (65%). Formalin-fixed, paraffin-embedded tissue was used for p16 staining (a surrogate marker for HPV) and testing for HPV DNA presence and type by Multiplex HPV PCR-MassArray. HPV DNA and/or p16 staining (HPV-positive) was found in 28.4% (150/528) tumors. p16 and HPV DNA were strongly correlated (F < 0.0001). HPV16 was present in 82.8%, and HPV58 in 7.5% of HPV-positive tumors. HPV was associated with higher age (55.5 vs. 52.7 years, p = 0.004), lower T-stage (p = 0.008) better overall survival (OS) (hazard ratio [HR] 0.58 [95% CI 0.42-0.81], p = 0.001), and disease-free survival (DFS) (HR 0.54 [95% CI 0.40-0.73], p < 0.0001). Alcohol was strongly associated with recurrence and death (OS: HR 2.06 [95% CI 1.54-2.74], p < 0.0001; DFS: HR 1.72 [95% CI 1.33-2.24], p < 0.0001). OS and DFS in HPV-positive cases decreased for alcohol users (p < 0.0001). Obscured by the strong alcohol effect, predictive associations were not found for tobacco or betel quid. CONCLUSIONS: As with HPV-positive OPSCC globally, HPV is an increasingly important etiological factor in Taiwanese OPSCC. HPV-positive OPSCC has considerable survival benefit, but this is reduced by alcohol, tobacco, and betel quid use. hrHPV is a cancer risk factor in males and females. Vaccinating both sexes with a multivalent vaccine including HPV58, combined with alcohol and tobacco cessation policies will be effective cancer-prevention public health strategies in Taiwan.

Head and Neck Paragangliomas: Patterns of Otolaryngology Referrals for Genetic Testing Over 2 Decades.

OBJECTIVE: A large proportion of head and neck paragangliomas (HNPGLs) arise in patients with a genetic predisposition due to pathogenic variants in succinate dehydrogenase (SDHx) genes. Contemporary practice guidelines recommend consideration of referral for genetic testing for all patients with HNPGLs. We sought to assess adherence to these recommendations, factors associated with referral, and temporal trends in referral patterns by otolaryngologists over the past 2 decades. STUDY DESIGN: Retrospective cohort study. SETTING: Single tertiary care center. METHODS: All patients with newly diagnosed HNPGLs treated at a single academic center between 2000 and 2019 were included. Bivariable association of specific features of referral for genetic testing by treating surgeons were tested with χ2 and Wilcoxon rank-sum tests. Logistic regression was used to assess temporal trends in referral patterns overall and for specific clinical subgroups over time. RESULTS: Of 221 patients included, only 77 (34.8%) were referred for genetic testing. Factors associated with referral included young age, family history of paraganglioma, more recent year of diagnosis (ie, closer to study end date), tumor subsite (all P < .0001), and treatment by an otolaryngologist (vs vascular surgeon or neurosurgeon, P = .009). Overall, referral rates increased over time (P = .0002), but even in the most recent 5 years, only 51% of newly diagnosed patients were referred. CONCLUSION: Our analysis suggests that referral rates for genetic testing in patients with HNPGLs are growing yet are still largely based on young age, family history, and tumor subsite.

Efficacy of axitinib in metastatic head and neck cancer with novel radiographic response criteria.

BACKGROUND: There are limited treatment options for unresectable recurrent or metastatic (R/M) head and neck squamous cell carcinoma (HNSCC). Vascular endothelial growth factor is of significant interest for targeted therapy in R/M HNSCC because of its central role in tumorigenesis and immunosuppression. Axitinib is a potent inhibitor of vascular endothelial growth factor receptor (VEGFR) 1 , VEGFR2, VEGFR3, platelet-derived growth factor receptor, as well as c-kit and offers such an approach. METHODS: This article reports the results of a phase 2 trial evaluating axitinib in R/M HNSCC according to the Choi criteria for radiographic response assessment. The primary endpoint of this trial was 6-month overall survival. RESULTS: Twenty-nine patients were enrolled, and 28 were evaluable for a response. Patients were heavily pretreated with 61% having had at least 1 previous systemic treatment in the metastatic setting (range, 0-5). The median overall survival of 9.8 months and the 6-month overall survival rate of 70% met the protocol-defined criteria for clinical efficacy. The best overall response rate was 42%. Correlative analyses demonstrated that PI3K signaling pathway alterations were associated with an increased response to therapy (75% vs 17%). A marked response to therapy was seen in a subgroup of patients who were treated with an immune checkpoint inhibitor after progression on axitinib. CONCLUSIONS: Treatment with axitinib is associated with improved survival in patients with heavily pretreated head and neck cancer, and PI3K pathway alterations may serve as a biomarker for response. Further investigation is warranted to evaluate axitinib in biomarker-selected populations, especially in combination with immune checkpoint inhibitor therapy. LAY SUMMARY: Metastatic head and neck squamous cancer is an incurable disease with limited treatment options and a poor prognosis. This study is the first to demonstrate that the targeted oral drug axitinib improves survival in patients with heavily pretreated metastatic head and neck cancer. Furthermore, patients whose tumors have specific mutations derive the greatest benefit from therapy. The investigation of axitinib alone or in combination with immunotherapy in a genomic biomarker-selected population is warranted.

Patient-reported financial toxicity and adverse medical consequences in head and neck cancer.

OBJECTIVES: Financial toxicity (FT) is a significant barrier to high-quality cancer care, and patients with head and neck cancer (HNCA) are particularly vulnerable given their need for intensive support, daily radiotherapy (RT), and management of long-term physical, functional, and psychosocial morbidities following treatment. We aim to identify predictors of FT and adverse consequences in HNCA following RT. MATERIALS AND METHODS: We performed a prospective survey study of patients with HNCA seen in follow-up at an academic comprehensive cancer center (CCC) or Veterans Affairs hospital between 05/2016 and 06/2018. Surveys included validated patient-reported functional outcomes and the COST measure, a validated instrument for measuring FT. RESULTS: The response rate was 86% (n = 63). Younger age and lower median household income by county were associated with lower COST scores (i.e., worse FT) on multivariable analysis (p = .045 and p = .016, respectively). Patients with worse FT were more likely to skip clinic visits (RR (95% CI) 2.13 (1.23-3.67), p = .007), be noncompliant with recommended supplements or medications (1.24 (1.03-1.48), p = .02), and require supportive infusions (1.10 (1.02-1.20), p = .02). At the CCC, patients with worse FT were more likely to require feeding tubes (1.62 (1.14-2.31), p = .007). Overall, 36% reported that costs were higher than expected, 48% were worried about paying for treatment, and 33% reported at least a moderate financial burden from treatment. CONCLUSION: HNCA patients experience substantial FT from their diagnosis and/or therapy, with potential implications for medical compliance, QOL, and survivorship care.

Soy Isoflavone Supplementation Increases Long Interspersed Nucleotide Element-1 (LINE-1) Methylation in Head and Neck Squamous Cell Carcinoma.

AIM: Soy isoflavones have been suggested as epigenetic modulating agents with effects that could be important in carcinogenesis. Hypomethylation of LINE-1 has been associated with head and neck squamous cell carcinoma (HNSCC) development from oral premalignant lesions and with poor prognosis. To determine if neoadjuvant soy isoflavone supplementation could modulate LINE-1 methylation in HNSCC, we undertook a clinical trial. METHODS: Thirty-nine patients received 2-3 weeks of soy isoflavone supplements (300 mg/day) orally prior to surgery. Methylation of LINE-1, and 6 other genes was measured by pyrosequencing in biopsy, resection, and whole blood (WB) specimens. Changes in methylation were tested using paired t tests and ANOVA. Median follow up was 45 months. RESULTS: LINE-1 methylation increased significantly after soy isoflavone (P < 0.005). Amount of change correlated positively with days of isoflavone taken (P = 0.04). Similar changes were not seen in corresponding WB samples. No significant changes in tumor or blood methylation levels were seen in the other candidate genes. CONCLUSION: This is the first demonstration of in vivo increases in tissue-specific global methylation associated with soy isoflavone intake in patients with HNSCC. Prior associations of LINE-1 hypomethylation with genetic instability, carcinogenesis, and prognosis suggest that soy isoflavones maybe potential chemopreventive agents in HNSCC.

Individualized survival prediction for patients with oropharyngeal cancer in the human papillomavirus era.

BACKGROUND: Accurate, individualized prognostication in patients with oropharyngeal squamous cell carcinoma (OPSCC) is vital for patient counseling and treatment decision making. With the emergence of human papillomavirus (HPV) as an important biomarker in OPSCC, calculators incorporating this variable have been developed. However, it is critical to characterize their accuracy prior to implementation. METHODS: Four OPSCC calculators were identified that integrate HPV into their estimation of 5-year overall survival. Treatment outcomes for 856 patients with OPSCC who were evaluated at a single institution from 2003 through 2016 were analyzed. Predicted survival probabilities were generated for each patient using each calculator. Calculator performance was assessed and compared using Kaplan-Meier plots, receiver operating characteristic curves, concordance statistics, and calibration plots. RESULTS: Correlation between pairs of calculators varied, with coefficients ranging from 0.63 to 0.90. Only 3 of 6 pairs of calculators yielded predictions within 10% of each other for at least 50% of patients. Kaplan-Meier curves of calculator-defined risk groups demonstrated reasonable stratification. Areas under the receiver operating characteristic curve ranged from 0.74 to 0.80, and concordance statistics ranged from 0.71 to 0.78. Each calculator demonstrated superior discriminatory ability compared with clinical staging according to the seventh and eighth editions of the American Joint Committee on Cancer staging manual. Among models, the Denmark calculator was found to be best calibrated to observed outcomes. CONCLUSIONS: Existing calculators exhibited reasonable estimation of survival in patients with OPSCC, but there was considerable variability in predictions for individual patients, which limits the clinical usefulness of these calculators. Given the increasing role of personalized treatment in patients with OPSCC, further work is needed to improve accuracy and precision, possibly through the identification and incorporation of additional biomarkers.

Implication of Fusobacterium necrophorum in recurrence of peritonsillar abscess.

OBJECTIVE: Peritonsillar abscess (PTA) is a common infectious complication of pharyngeal infection managed by otolaryngologists and emergency room physicians. Streptococcus and Fusobacterium (e.g., Fusobacterium necrophorum, FN) species are commonly isolated pathogens. The aim of this study was to determine the implication of culture results on abscess recurrence following drainage. METHODS: Single-institution retrospective review of patients treated at the University of Michigan between 2000 and 2017. Demographic and clinical outcome data were analyzed, including treatment details, culture data, and recurrence. RESULTS: One hundred fifty-six of the 990 patients in our study developed recurrence of their abscess (16%). The age ranges most susceptible to recurrence included adolescent (22.9%) and young adult groups (17.1%). Recurrent patients were more likely to have experienced acute progression of symptoms (79% vs. 71%, P = 0.03), trismus (67% vs. 55%, P = 0.006), voice changes (65% vs. 57%, P = 0.04), and dysphagia (72% vs. 61%, P = 0.01) compared to nonrecurrent patients. They were also more likely to have clinical lymphadenopathy noted on initial examination (67% vs. 56%, P = 0.009). Culture data was sent for 852 patients (86%). The presence of FN was significantly more prevalent in the recurrent group (P < 0.0001). CONCLUSION: There is a high observed prevalence of FN species within PTA aspirates in the recurrent PTA population. PTA aspirate should be sent for anaerobic growth to screen for Fusobacterium species. In addition, follow-up and lower threshold for subsequent tonsillectomy should be considered in this at-risk group. LEVEL OF EVIDENCE: 3 Laryngoscope, 129:1567-1571, 2019.

Predictors of intratonsillar versus peritonsillar abscess: A case-control series.

OBJECTIVES/HYPOTHESIS: An uncommon phenomenon in relation to the peritonsillar abscess (PTA) is the intratonsillar abscess (ITA) or formation of an abscess within tonsillar parenchyma. This study sought to characterize our experience with diagnosis and management of ITAs in the context of the PTA patient population. STUDY DESIGN: Case-control series. METHODS: This is a single-institution retrospective review of patients treated at the University of Michigan between 2000 and 2017. RESULTS: Six hundred fifty-five adult patients were identified. The incidence of ITA within the PTA population was 7% (n = 43). Patients with ITA had lower mean white blood cell count (P = .03), lower proportion of trismus (P < .0001), otalgia (P = .007), vocal changes (P < .0001), and fewer incidences of acute progression of symptoms (P = .0007). On multivariable analysis, ITA patients were noted to be older, present with a longer duration of symptoms, and have greater incidence of neck pain and lymphadenopathy. Drainage was attempted in fewer ITA patients and was rarely successful (15%) in comparison to successful drainage for PTA patients (69%) (P < .0001). CONCLUSIONS: Symptomatology differs for ITA, as fewer present with the classic PTA symptoms of otalgia, trismus, and voice alterations. The lack of classic symptoms likely leads to delayed presentation. A greater number of ITA patients presented with neck pain and lymphadenopathy. In the ITA population, aspiration attempts were more infrequent and less successful in yielding purulence. Given infrequent yield of pus and low overall recurrence rate, the diagnosing clinician should consider medical management in this distinct patient population. LEVEL OF EVIDENCE: 4 Laryngoscope, 129:1354-1359, 2019.

Predictors of intratonsillar abscess versus peritonsillar abscess in the pediatric patient.

OBJECTIVE: To determine the incidence of intratonsillar abscess (ITA) patients within the population of patients diagnosed with peritonsillar abscess (PTA) and to further characterize the differences in symptomatology and successful treatment strategies between the two groups. METHODS: This study is a retrospective chart review of patients diagnosed with PTA or ITA at our institution from 2000 to 2017. Descriptive and inferential statistics are reported, including univariate and multivariate analyses. RESULTS: A total of 335 pediatric (<18 years) patients presenting with a PTA or ITA were identified, 31 (9%) of whom were diagnosed with ITA. Patients with ITAs had significantly lower proportions of trismus, otalgia, and dysphagia and were less likely to experience acute progression from their initial symptoms. The ITA group had fewer attempted aspiration and drainage attempts, with those attempts significantly less successful than for the PTA group. Recurrence was uncommon in ITA patients in comparison to PTA patients. CONCLUSIONS: Intratonsillar abscess should be considered in the differential diagnosis for patients presenting with sore throat and concern for a pharyngeal infection or abscess. These patients have a significantly lower proportion of otalgia, trismus, vocal changes, and dysphagia. Given the low success rate of drainage attempts and lower recurrence rate, diagnosing physicians should consider medical management rather than procedural drainage in this patient population.

Prognostic Value of FDG-PET/CT Metabolic Parameters in Metastatic Radioiodine-Refractory Differentiated Thyroid Cancer.

PURPOSE: There are no standardized prognostication algorithms for metastatic radioiodine-refractory (RAI-R) differentiated thyroid cancer (DTC). We hypothesize that [F]-FDG PET/CT may predict progression versus stability of disease based on quantitative analysis of metabolic tumor volume (MTV) and total lesion glycolysis (TLG). METHODS: Retrospective study of 62 patients with metastatic RAI-R DTC to determine clinical outcomes with median follow-up from initial diagnosis of 11.1 years (8.38, 14.1) (range, 1.2-20 years). Baseline [F]-FDG PET/CT scans were evaluated qualitatively for regional and distant metastases and quantitatively for tumor burden based on MTV and TLG obtained using gradient segmentation method. RESULTS: After diagnosis of metastatic RAI-R disease was established, the 5-year overall survival (OS) probability was 34%, and median OS was 3.56 years (2.87, infinity). The 5-year progression-free survival (PFS) probability was 19%, and median PFS was 1.31 years (1.03, 2.38). TSH-suppressed thyroglobulin (Tg) levels greater than 100 ng/mL and Tg doubling time (Tg-DT) less than 6 months were significantly associated with worse OS and PFS. Higher than median values of MTV and TLG were associated with worse OS (P = 0.06) and PFS (P = 0.007). Higher hazard of death was noted for higher values of log-MTV and log-TLG (HR, 1.17 [95% confidence interval, 0.99-1.39], P = 0.05, and HR, 1.14 [95% confidence interval, 1.00-1.31], P = 0.05, respectively). CONCLUSIONS: [F]-FDG PET/CT metabolic parameters can help define the volume and biologic variations of metastatic tumor burden. Metabolic tumor volume and TLG can be used for dynamic risk stratification of patients with metastatic RAI-R DTC regarding PFS and complement Tg-DT for prognosis of clinical disease course.