Definitive Radiotherapy versus Surgery for the Treatment of Verrucous Carcinoma of the Larynx: A National Cancer Database Study

Abstract Introduction Traditionally, larger lesions of laryngeal verrucous carcinoma are treated with surgical excision, with definitive radiotherapy generally reserved for smaller lesions. However, data utilizing modern databases is limited. Objective The authors sought to assess, utilizing the National Cancer Database, whether overall survival for patients with laryngeal verrucous carcinoma was equivalent when treated with definitive radiotherapy versus definitive surgery. Methods A retrospective cohort study was conducted utilizing the National Cancer Database. All cases of laryngeal verrucous carcinoma within the National Cancer Database between 2006 and 2014 were reviewed. Patients with T1-T3 (American Joint Commission on Cancer 7th Edition) laryngeal verrucous carcinoma were included and stratified by treatment modality. Demographics, treatment, and survival data were analyzed. Results A total of 392 patients were included. Two hundred and fifty patients underwent surgery and 142 received radiotherapy. The two groups differed in age, transition of care, clinical T stage, and clinical stages. There was no significant difference in survival between T1-T3 lesions treated with surgery or radiotherapy (p =0.32). Age, comorbidities, insurance status, and clinical T stage impacted overall hazard on multivariate analysis (p <0.01). For patients treated with radiotherapy, age, insurance status, and clinical T stage were predictive of increased hazard. Conclusion Overall survival is equivalent for patients with clinical T1 and clinical T2 laryngeal verrucous carcinoma treated with primary radiotherapy versus primary surgery. Thus, radiotherapy should be considered as a non-inferior treatment modality for certain patients with laryngeal verrucous carcinoma.

Definitive Radiotherapy versus Surgery for the Treatment of Verrucous Carcinoma of the Larynx: A National Cancer Database Study.

Introduction Traditionally, larger lesions of laryngeal verrucous carcinoma are treated with surgical excision, with definitive radiotherapy generally reserved for smaller lesions. However, data utilizing modern databases is limited. Objective The authors sought to assess, utilizing the National Cancer Database, whether overall survival for patients with laryngeal verrucous carcinoma was equivalent when treated with definitive radiotherapy versus definitive surgery. Methods A retrospective cohort study was conducted utilizing the National Cancer Database. All cases of laryngeal verrucous carcinoma within the National Cancer Database between 2006 and 2014 were reviewed. Patients with T1-T3 (American Joint Commission on Cancer 7th Edition) laryngeal verrucous carcinoma were included and stratified by treatment modality. Demographics, treatment, and survival data were analyzed. Results A total of 392 patients were included. Two hundred and fifty patients underwent surgery and 142 received radiotherapy. The two groups differed in age, transition of care, clinical T stage, and clinical stages. There was no significant difference in survival between T1-T3 lesions treated with surgery or radiotherapy ( p = 0.32). Age, comorbidities, insurance status, and clinical T stage impacted overall hazard on multivariate analysis ( p < 0.01). For patients treated with radiotherapy, age, insurance status, and clinical T stage were predictive of increased hazard. Conclusion Overall survival is equivalent for patients with clinical T1 and clinical T2 laryngeal verrucous carcinoma treated with primary radiotherapy versus primary surgery. Thus, radiotherapy should be considered as a non-inferior treatment modality for certain patients with laryngeal verrucous carcinoma.

Systematic review of neuroendocrine carcinomas of the oropharynx.

Data describing features and management of oropharyngeal neuroendocrine carcinomas (NEC) remain sparse. A systematic review was performed. Patients were stratified by treatment modality and examined for disease progression and survival outcomes. Ninety-four patients from 50 publications were included. Average age at diagnosis was 59.7 years (range 14-83). 73.4% were male. Most studies did not document HPV status. Forty patients (85.1%) were p16 positive, and 34 (85.0%) were HPV-ISH positive. Overall survival was 75.4% at 1 year, and 40.0% at 2 years. Of patients with locoregional disease, 33.8% developed distant metastasis. 12.5% of patients developed locoregional recurrence. Patients who developed distant metastases had worse overall survival (p = 0.0004). No significant difference was found between treatment modalities. Human papilloma virus may be associated with oropharyngeal NEC. Current treatments provide locoregional control, but distant metastases are common and confer low overall survival.

Cutaneous hyperpigmentation following bleomycin sclerotherapy for vascular malformations.

Systemic bleomycin therapy is associated with pulmonary fibrosis and cutaneous side effects. While it is believed that there is little to no systemic distribution of bleomycin when utilized to treat vascular malformations (VMs), we present a case series in which cutaneous, adhesive-related hyperpigmentation suggests that there is systemic egress of bleomycin following direct puncture sclerotherapy (DPS). This risk of hyperpigmentation after intralesional bleomycin should be discussed with patients, and steps to minimize the chances of it occurring should be implemented.

The outcomes of hypoglossal nerve stimulation in the management of OSA: A systematic review and meta-analysis.

OBJECTIVES: Obstructive sleep apnea (OSA) is a prevalent disease with significant health impacts. While first line therapy is CPAP, long-term compliance is low and device misuse is common, highlighting the need for alternative therapies. Upper airway surgery is one alternative, but substantial side effects hamper efficacy. A new alternative is an implantable hypoglossal nerve stimulator (HNS). These devices utilize neuromodulation to dilate/reinforce the airway and reduce side effects associated with traditional surgery. Several recent trials investigated the efficacy of these devices. The purpose of this study was to perform meta-analysis of available HNS studies investigating treatment of OSA to analyze objective and subjective outcomes and side effects. METHODS: A comprehensive literature search of PubMed and Scopus was performed. Two independent reviewers examined clinical trials investigating HNS in treatment of sleep apnea in adults. Studies with objective and subjective endpoints in sleep were included for analysis. Adverse events from trials were also recorded. RESULTS: Across 16 studies, 381 patients were analyzed. At 6 months (p = 0.008), mean SAQLI improved by 3.1 (95%CI, 2.6-3.7). At 12 months (p < 0.0001), mean AHI was reduced by 21.1 (95%CI, 16.9-25.3), mean ODI was reduced by 15.0 (95%CI, 12.7-17.4), mean ESS was reduced by 5.0 (95%CI, 4.2-5.8), mean FOSQ improved by 3.1 (95%CI, 2.6-3.4). Pain (6.2%:0.7-16.6), tongue abrasion (11.0%:1.2-28.7), and internal (3.0%:0.3-8.4)/external device (5.8%:0.3-17.4) malfunction were common adverse events. CONCLUSIONS: HNS is a safe and effective treatment for CPAP refractory OSA. Further study comparing HNS to other therapies is required.

Gland-preserving surgery for salivary stones and the utility of sialendoscopes.

BACKGROUND: Sialoendoscopy is the standard treatment for sialolithiasis; however, some patients may be unlikely to benefit from an endoscopic approach. This study assesses predictors of failure in the endoscopic management of sialoliths. METHODS: Patients treated for sialolithiasis from 2012 to 2017 at two centers were stratified into 3 groups: successful interventional sialendoscopy, incisional sialolithotomy, and gland excision. Patient, disease, and surgical factors were compared. RESULTS: Interventional sialendoscopy was attempted in 156 of 206 cases and successful for 42 (27%). Endoscopically retrieved calculi were smaller (4.96 mm) compared to incisional sialolithotomy (7.90 mm). Nonendoscopic approaches were required more often in submandibular cases 87% (P ≤ .005). Palpable stones were present in 74% of incisional sialolithotomies (P < .001). Submandibular location (OR 3.50, 1.53-7.98), palpability (OR 2.74, 1.21-6.18), CT localization (OR 3.05, 1.32-7.10, P = .010), and increased diameter (OR 1.25, 1.09-1.44) were predictive of incisional management. CONCLUSION: Stone size/location, CT-localization, and palpability were predictive of calculi that require an incisional approach. If these factors are recognized, the surgeon can consider proceeding directly to incisional sialolithotomy. LEVEL OF EVIDENCE: III.

Prognostic Impact of High-Risk Pathologic Features in HPV-Related Oropharyngeal Squamous Cell Carcinoma and Tobacco Use.

OBJECTIVES: To assess the impact of pathologic features and chronic tobacco use on human papillomavirus (HPV)-related oropharyngeal squamous cell carcinoma (OPSCC). STUDY DESIGN: Case series with chart review. SETTING: Single tertiary care referral center. SUBJECT AND METHODS: A total of 301 patients were treated for OPSCC from 2008 to 2016. Clinical and pathologic T and N stage, American Joint Committee on Cancer (AJCC) stage (seventh and eighth edition staging manuals), cigarette pack years, alcohol use, and presence of extranodal extension (ENE), perineural invasion (PNI), or lymphovascular invasion (LVI) were assessed. Patients were stratified into HPV negative, HPV-positive heavy smokers (≥20 pack years), and HPV-positive nonsmokers. Five-year survival by Kaplan-Meier method was assessed. RESULTS: Of the HPV-positive patients, 97 were nonsmokers and 73 were heavy smokers. HPV-positive heavy smokers had significantly decreased survival compared to their nonsmoking counterparts ( P = .02). The presence of ENE was associated with a significantly decreased 5-year survival ( P = .02) in heavy smokers relative to nonsmokers in HPV-positive patients. Furthermore, for the AJCC eighth edition, clinically stage 1 HPV-positive heavy smokers had significantly decreased survival relative to nonsmokers ( P = .01). CONCLUSIONS: This series highlights the potential need for more aggressive therapy for HPV-positive patients with extensive tobacco use under the new staging system.

Association of Treatment Delays With Survival for Patients With Head and Neck Cancer: A Systematic Review.

Importance: Delays in the delivery of care for head and neck cancer (HNC) are a key driver of poor oncologic outcomes and thus represent an important therapeutic target. Objective: To synthesize information about the association between delays in the delivery of care for HNC and oncologic outcomes. Evidence Review: A systematic review of the English-language literature in PubMed/MEDLINE and Scopus published between January 1, 2007, and February 28, 2018, was performed to identify articles addressing the association between treatment delays and oncologic outcomes for patients with HNC. Articles that were included (1) addressed cancer of the oral cavity, oropharynx, hypopharynx, or larynx; (2) discussed patients treated in 2004 or later; (3) analyzed time of diagnosis to treatment initiation (DTI), time from surgery to the initiation of postoperative radiotherapy, and/or treatment package time (TPT; the time from surgery through the completion of postoperative radiotherapy); (4) included a clear definition of treatment delay; and (5) analyzed the association between the treatment time interval and an oncologic outcome measure. Quality assessment was performed using the Institute of Health Economics Quality Appraisal Checklist for Case Series Studies. Findings: A total of 18 studies met inclusion criteria and formed the basis of the systematic review. Nine studies used the National Cancer Database and 6 studies were single-institution retrospective reviews. Of the 13 studies assessing DTI, 9 found an association between longer DTI and poorer overall survival; proposed DTI delay thresholds ranged from more than 20 days to 120 days or more. Four of the 5 studies assessing time from surgery to the initiation of postoperative radiotherapy (and all 4 studies assessing guideline-adherent time to postoperative radiotherapy) found an association between a timely progression from surgery to the initiation of postoperative radiotherapy and improved overall or recurrence-free survival. Of the 5 studies examining TPT, 4 found that prolonged TPT correlated with poorer overall survival; proposed thresholds for prolonged TPT ranged from 77 days or more to more than 100 days. Conclusions and Relevance: Timely care regarding initiation of treatment, postoperative radiotherapy, and TPT is associated with survival for patients with HNC, although significant heterogeneity exists for defining delayed DTI and TPT. Further research is required to standardize optimal time goals, identify barriers to timely care for each interval, and design interventions to minimize delays.

Cryotherapy for the Treatment of Chronic Rhinitis: A Qualitative Systematic Review.

BACKGROUND: Chronic rhinitis impacts 60 million Americans and is associated with significant costs for patients. Although medical treatments are first line, some patients require surgical intervention such as vidian or posterial nasal neurectomy. Previous reviews have investigated the role of surgical management in chronic rhinitis, but none have investigated a longstanding treatment with recent interest: cryotherapy. OBJECTIVE: To identify the safety, efficacy, and durability of treatment response of cryotherapy in treating chronic rhinitis. METHODS: A systematic literature review was performed to identify studies that investigated the utility of cryotherapy in chronic rhinitis. Only studies with the primary objective of assessing the efficacy of cryotherapy on chronic rhinitis were included. Patients were classified as allergic rhinitis, nonallergic rhinitis (vasomotor rhinitis), or mixed rhinitis using the original author's criteria. Data were extracted regarding reported complications, treatment efficacy, and length of follow-up. RESULTS: A total of 110 abstracts were identified, of which 15 were included in this review. Epistaxis and nasal obstruction were commonly reported complications. No serious adverse events were reported. For obstructive symptoms, "reduced" symptoms were reported in 63.4% to 100% of patients. In regard to rhinorrhea, reports of reduced symptoms were experienced from 77% to 100% of patients. Seven studies used only patient-reported improvements without stratifying results based on symptom type; general improvements ranged from 67% to 100%. Nine studies noted symptom improvement in nonallergic cohorts ranging from 67% to 97.5% of patients. Four studies noted improvement in allergic cohorts ranging from 63.4% to 80% of patients. Two studies noted improvement in patients with mixed pictures ranging from 92.5% to 100%. CONCLUSIONS: Although cryotherapy appears safe and efficacious, heterogeneous past investigations with low-quality evidence make strong, evidence-based recommendations difficult to make. Further study with validated metrics and controlled populations is certainly warranted and should be encouraged.

The Sinus and Nasal Quality of Life Survey (SN-5) in the Management of Pediatric Chronic Rhinosinusitis: A systematic review and meta-analysis.

OBJECTIVES: Pediatric chronic rhinosinusitis (CRS) is a prevalent condition with quality of life (QoL) impacts that are seldom reported in the literature. We aimed to conduct a systematic review and meta-analysis on studies using the Sinus and Nasal Quality of Life Survey (SN-5), the only validated symptom questionnaire in pediatric CRS. METHODS: A literature search was conducted to identify studies that used the SN-5 to measure QoL before and after medical or surgical interventions for pediatric CRS. Comparison of means and standard deviations was performed between pre- and post-intervention SN-5 scores. RESULTS: A total of 10 studies, consisting of 13 separate treatment arms of either medical therapy, adenoidectomy, balloon catheter sinuplasty (BCS), or functional endoscopic sinus surgery (FESS) were identified. The vast majority (92.3%) of the treatment arms demonstrated minimal clinically important differences between baseline and post-intervention SN-5 scores. Rates of treatment success and minimal clinically important difference among all treatment arms ranged from 43.2% to 94.0%. Comparison of means showed an improvement in SN-5 score of 1.97 [95% CI, 1.18 to 2.76; p < 0.00001] for BCS, 1.83 [95% CI, 1.47 to 2.19; p < 0.00001] for FESS, and 1.15 [95% CI, 0.36 to 2.66; p = 0.13) for medical treatment. CONCLUSION: There is a paucity of literature on QoL outcomes in pediatric CRS. More studies using the SN-5, particularly those controlling for baseline patient characteristics, are necessary to fully elucidate the impact of various interventions on QoL in pediatric CRS.

The liquid biopsy in lung cancer.

The incidence of lung cancer has significantly increased over the last century, largely due to smoking, and remains the most common cause of cancer deaths worldwide. This is often due to lung cancer first presenting at late stages and a lack of curative therapeutic options at these later stages. Delayed diagnoses, inadequate tumor sampling, and lung cancer misdiagnoses are also not uncommon due to the limitations of the tissue biopsy. Our better understanding of the tumor microenvironment and the systemic actions of tumors, combined with the recent advent of the liquid biopsy, may allow molecular diagnostics to be done on circulating tumor markers, particularly circulating tumor DNA. Multiple liquid biopsy molecular methods are presently being examined to determine their efficacy as surrogates to the tumor tissue biopsy. This review will focus on new liquid biopsy technologies and how they may assist in lung cancer detection, diagnosis, and treatment.