Phase I study of nab-paclitaxel-based induction followed by nab-paclitaxel-based concurrent chemotherapy and re-irradiation in previously treated head and neck squamous cell carcinoma.

BACKGROUND: Recurrent head and neck squamous cell carcinoma (HNSCC) is associated with poor overall survival (OS). Prior studies suggested incorporation of nab-paclitaxel (A) may improve outcomes in recurrent HNSCC. METHODS: This Phase I study evaluated induction with carboplatin and A followed by concomitant FHX (infusional 5-fluorouracil, hydroxyurea and twice-daily radiation therapy administered every other week) plus A with cohort dose escalation ranging from 10-100 mg/m2 in recurrent HNSCC. The primary endpoint was maximally tolerated dose (MTD) and dose-limiting toxicity (DLT) of A when given in combination with FHX (AFHX). RESULTS: Forty-eight eligible pts started induction; 28 pts started AFHX and were evaluable for toxicity. Two DLTs occurred (both Grade 4 mucositis) at a dose level 20 mg/m2. No further DLTs were observed with subsequent dose escalation. The MTD and recommended Phase II dose (RP2D) of A was 100 mg/m2. CONCLUSIONS: In this Phase I study, the RP2D of A with FHX is 100 mg/m2 (AFHX). The role of re-irradiation with immunotherapy warrants further investigation. CLINICAL TRIAL INFORMATION: This clinical trial was registered with ClinicalTrials.gov identifier: NCT01847326.

Large non-functioning substernal parathyroid cyst: A case report and review of the literature.

OBJECTIVES: Parathyroid cysts are rare benign lesions of the head and neck that account for less than 1% of cystic neck masses. We present a rare case of a large 6 cm substernal parathyroid cyst. PRESENTATION OF CASE: An otherwise healthy 65 year-old female presented to the otolaryngology clinic for evaluation of an anterior, midline neck mass. On physical exam, she was noted to have a fullness in the anterior neck extending to the sternal notch. CT demonstrated an enlarged thyroid with a cyst extending to the aortic arch. Initial evaluation suggested a bilateral goiter with substernal extension. The cyst was managed with drainage and observation. After two years of continued growth, the patient underwent a left thyroid lobectomy and mediastinal mass resection via the cervical approach. Final pathology was consistent with a parathyroid cyst. CONCLUSIONS: Parathyroid cysts are a rare cause of neck mass in an adult, and a 6 cm substernal parathyroid cyst represents an unusual site and size for these cysts. Parathyroid cysts are not often considered on the differential of neck and mediastinal cystic lesions. However, appropriate steps should be taken to ensure a proper diagnosis for any cystic lesion in the neck.

Dose and Volume De-Escalation for Human Papillomavirus-Positive Oropharyngeal Cancer is Associated with Favorable Posttreatment Functional Outcomes.

PURPOSE: To report functional outcomes for patients with human papillomavirus-positive oropharyngeal cancer treated on a phase 2 protocol of risk- and induction chemotherapy response-adapted dose and volume de-escalated radiation therapy (RT)/chemoradiation (CRT). METHODS AND MATERIALS: Patients were stratified as low risk (LR) or high risk (HR) according to T/N-stage and smoking history. Induction chemotherapy was followed by radiographic response assessment. LR patients with ≥50% response received 50 Gy RT (RT50), whereas LR patients with 30% to 50% response or HR patients with ≥50% response received 45 Gy CRT (CRT45). All other patients received 75 Gy CRT (CRT75) with RT limited to the first echelon of uninvolved nodes. Pre- and post-RT/CRT modified barium swallow studies were performed. Percutaneous endoscopic gastrostomy (PEG) tube placement, body mass index (BMI), and narcotic use were recorded. Statistical comparisons used linear or logistic regression, the Mann-Whitney U test, the χ2 test, or Fisher's exact test as appropriate. RESULTS: Twenty-eight LR and 34 HR patients were enrolled; 49 completed RT50/CRT45 and 11 completed CRT75. PEG-tube dependency at the end of RT/CRT and 3 months post-RT/CRT significantly differed according to risk and treatment groups (all P < .05). Treatment intensity was independently associated with 3-month PEG status while adjusting for risk group (P = .002). The CRT75 group had a median -8.42% change from baseline BMI at 1 year post-RT/CRT versus -2.54% for the RT50/CRT45 group (P = .01). At the end of RT/CRT, CRT75 patients were less likely to tolerate a normal diet, more likely to have swallowing performance status scale scores ≥4, more likely to have Rosenbek's penetration-aspiration scores ≥7, more likely to have developed trismus, and more likely to require narcotics >2 months (all P < .05). CONCLUSIONS: Induction chemotherapy followed by risk- and response-adapted dose and volume de-escalated RT/CRT is associated with clinically meaningful functional outcomes including (1) improved swallowing function, (2) higher BMI, and (3) shorter narcotic use for patients receiving de-escalation.

A Surgical Safety Checklist for Performing Tracheotomy in Patients with Coronavirus Disease 19.

Performance of tracheotomy is a potential necessary step in the patient with coronavirus disease 19 (COVID-19) and prolonged mechanical ventilation. Due to viral aerosolization, tracheotomy carries a high risk of transmission of COVID-19 to the health care team performing the procedure. We share our institution's surgical safety checklist for performing tracheotomy in patients with COVID-19, including key modifications intended to mitigate risk to the surgical team.

Pituitary Adenoma Deposit in the Nasolabial Region Following Sublabial Transsphenoidal Surgery in the Setting of Nelson Syndrome.

Pituitary adenomas are a group of tumors arising from the anterior pituitary gland, and with the exception of prolactin-secreting adenomas, transsphenoidal resection is the cornerstone of treatment. Although most adenomas are located within the pituitary fossa, ectopic adenomas have been reported, primarily occurring along the route of embryologic development. In this article, we present the case of an ectopic pituitary adenoma in the nasolabial fold that likely resulted from seeding during transsphenoidal resection via sublabial approach.

Definitive chemoradiation for locally-advanced oral cavity cancer: A 20-year experience.

OBJECTIVES: Definitive chemoradiation (CRT) for oral cavity squamous cell carcinoma (OC-SCC) is often criticized for poor efficacy or toxicity. We describe a favorable 20-year experience of primary CRT for locally-advanced OC-SCC. MATERIALS AND METHODS: Patients with locally-advanced, stage III/IV OC-SCC receiving primary concomitant CRT on protocols from 1994 to 2014 were analyzed. Chemotherapy included fluorouracil and hydroxyurea with other third agents. Radiotherapy (RT) was delivered once or twice daily to a maximum dose of 70-75 Gy. Intensity-modulated RT (IMRT) was exclusively used after 2004. Progression-free survival (PFS), overall survival (OS), locoregional control (LRC), and distant control (DC) were calculated by the Kaplan-Meier method and compared across treatment decades using the log-rank test. Rates of osteoradionecrosis (ORN) requiring surgery were compared across treatment decades using the Chi-square test. RESULTS: 140 patients with locally-advanced OC-SCC were treated with definitive CRT. Of these, 75.7% had T3/T4 disease, 68.6% had ≥N2 nodal disease, and 91.4% had stage IV disease. Most common primary sites were oral tongue (47.9%) and floor of mouth (24.3%). Median follow-up was 5.7 years. Five-year OS, PFS, LRC, and DC were 63.2%, 58.7%, 78.6%, and 87.2%, respectively. Rates of ORN and long-term feeding tube dependence were 20.7% and 10.0%, respectively. Differences in LRC (P = 0.90), DC (P = 0.24), PFS (P = 0.38), OS (P = 0.10), or ORN (P = 0.38) were not significant across treatment decades. CONCLUSION: Definitive CRT is a viable and feasible strategy for organ preservation for patients with locally-advanced OC-SCC.

Role of dental hardware in oral cavity squamous cell carcinoma in the low-risk nonsmoker nondrinker population.

BACKGROUND: Oral cavity squamous cell carcinoma (SCC) arising in nonsmokers and nondrinkers remains poorly characterized. We hypothesized that these patients had prior exposure to metallic dental hardware. METHODS: We utilized a questionnaire querying the lifetime oral health status of 54 patients. Demographics and extensive oral health history were collected. RESULTS: The majority of patients (74%) had prior exposure to metallic dental hardware. The younger population with almost exclusively oral tongue cancer had a high prevalence of metallic orthodontic braces (40%) within 15 years before diagnosis. In the 51+ year age group, 82% had crowns, dental implants, and/or dentures with metallic elements. CONCLUSION: Exposure to metallic dental hardware has increased in the past few decades given the rise of orthodontic braces and older adults retaining more teeth. Although this study does not prove a causal relationship between oral cavity SCC and dental hardware, this is a step toward identifying and investigating their role.

Laryngotracheal Involvement in Systemic Light Chain Amyloidosis.

Laryngotracheal amyloid deposition is an uncommon manifestation of systemic light chain amyloidosis. Diagnostic imaging, such as CT, is useful for suggesting the possibility of amyloidosis and delineating the extent of the lesions for surgical management; however, the diagnosis is confirmed with the histologic finding of amorphous eosinophilic material which stains positively for Congo red and may show apple green birefringence on polarization. These features are exemplified in this sine qua non radiology-pathology correlation article.

AHNS Series - Do you know your guidelines? Principles of treatment for glottic cancer: A review of the National Comprehensive Cancer Network guidelines.

This article is a continuation of the "Do You Know Your Guidelines" series, an initiative of the American Head and Neck Society's Education Committee to increase awareness of current best practices pertaining to head and neck cancer. The National Comprehensive Cancer Network (NCCN) guidelines for primary and adjuvant treatment of cancer of the glottic larynx are reviewed here in a systematic fashion according to stage.

AHNS Series - Do you know your guidelines? Principles of treatment for nasopharyngeal cancer: A review of the National Comprehensive Cancer Network guidelines.

This article is a continuation of the "Do You Know Your Guidelines" series, an initiative of the American Head and Neck Society's Education Committee to increase awareness of current best practices pertaining to head and neck cancer. The National Comprehensive Cancer Network guidelines for the management of nasopharyngeal cancer are reviewed here in a systematic fashion. These guidelines outline the workup, treatment and surveillance of patients with nasopharyngeal cancer. © 2016 Wiley Periodicals, Inc. Head Neck 39: 201-205, 2017.

Integrative and comparative genomic analysis of HPV-positive and HPV-negative head and neck squamous cell carcinomas.

PURPOSE: The genetic differences between human papilloma virus (HPV)-positive and -negative head and neck squamous cell carcinomas (HNSCC) remain largely unknown. To identify differential biology and novel therapeutic targets for both entities, we determined mutations and copy-number aberrations in a large cohort of locoregionally advanced HNSCC. EXPERIMENTAL DESIGN: We performed massively parallel sequencing of 617 cancer-associated genes in 120 matched tumor/normal samples (42.5% HPV-positive). Mutations and copy-number aberrations were determined and results validated with a secondary method. RESULTS: The overall mutational burden in HPV-negative and HPV-positive HNSCC was similar with an average of 15.2 versus 14.4 somatic exonic mutations in the targeted cancer-associated genes. HPV-negative tumors showed a mutational spectrum concordant with published lung squamous cell carcinoma analyses with enrichment for mutations in TP53, CDKN2A, MLL2, CUL3, NSD1, PIK3CA, and NOTCH genes. HPV-positive tumors showed unique mutations in DDX3X, FGFR2/3 and aberrations in PIK3CA, KRAS, MLL2/3, and NOTCH1 were enriched in HPV-positive tumors. Currently targetable genomic alterations were identified in FGFR1, DDR2, EGFR, FGFR2/3, EPHA2, and PIK3CA. EGFR, CCND1, and FGFR1 amplifications occurred in HPV-negative tumors, whereas 17.6% of HPV-positive tumors harbored mutations in fibroblast growth factor receptor genes (FGFR2/3), including six recurrent FGFR3 S249C mutations. HPV-positive tumors showed a 5.8% incidence of KRAS mutations, and DNA-repair gene aberrations, including 7.8% BRCA1/2 mutations, were identified. CONCLUSIONS: The mutational makeup of HPV-positive and HPV-negative HNSCC differs significantly, including targetable genes. HNSCC harbors multiple therapeutically important genetic aberrations, including frequent aberrations in the FGFR and PI3K pathway genes. See related commentary by Krigsfeld and Chung, p. 495.

Chemoradiation for patients with large-volume laryngeal cancers.

BACKGROUND: Patients with T4 laryngeal cancers, including those with large-volume (cartilage or tongue-base invasion) lesions, are often excluded from organ-preservation trials due to expectations of inferior outcome in terms of survival and function. We hypothesize that such patients indeed have acceptable survival and function when treated with organ-preservation strategies. METHODS: Retrospective analysis of prospectively collected data of a cohort of patients with T4 laryngeal cancer was carried out. Follow-up ranged from 0.18 to 15.6 years. All T4 laryngeal cancer patients who were enrolled in the University of Chicago concomitant chemoradiotherapy protocols from 1994 to the present were reviewed. This study was composed of 80 newly diagnosed T4 laryngeal cancer patients. Efficacy of treatment was determined through evaluations of survival and function. Survival was evaluated via Kaplan-Meier methods. Swallowing function was evaluated by an oropharyngeal motility (OPM) study and swallowing scores were assigned. Higher scores reflected increasing swallowing dysfunction. RESULTS: Fifty-five of 80 patients (~69%) had documented large-volume tumor. Two- and 5-year overall survivals were 60.0% and 48.7%, respectively. Disease-specific 2- and 5-year survivals for the group were 80.1% and 71.3%, and 79.4 and 74.3%, respectively, for the 55 patients with large volume status. Progression-free survival rates were 52.6% and 47.6%. Forty-four of 65 patients (~68%) with OPM data had a Swallowing Performance Status Scale (SPSS) score of ≤5, indicating various degrees of swallowing abnormalities not requiring a gastrostomy tube. This is a functional-preservation rate of 67.7%. CONCLUSIONS: Chemoradiation for patients with T4 laryngeal cancer appears to be an effective and reasonable option, particularly in light of the satisfactory survival and function-preservation rates.

Adjuvant chemoradiotherapy for locoregionally advanced and high-risk salivary gland malignancies.

BACKGROUND: To report the outcomes of patients with locoregionally advanced and high- risk salivary gland malignancies treated with surgery followed by adjuvant chemoradiotherapy. METHODS: From 09/1991 - 06/2007, 24 high-risk salivary gland cancer patients were treated with surgery, followed by adjuvant chemoradiotherapy for high-risk pathologic features including, perineural involvement, nodal involvement, positive margins, or T3/T4 tumors. Chemoradiotherapy was delivered for 4-6 alternating week cycles: the most common regimen, TFHX, consisted of 5 days paclitaxel (100 mg/m² on d1), infusional 5-fluorouracil (600 mg/m²/d × 5d), hydroxyurea (500 mg PO BID), and 1.5 Gy twice daily irradiation followed by a 9-day break without treatment. RESULTS: Median follow-up was 42 months. The parotid gland was more frequently involved (n = 17) than minor (n = 4) or submandibular (n = 3) glands. The median radiation dose was 65 Gy (range 55-68 Gy). Acute treatment related toxicity included 46% grade 3 mucositis and 33% grade 3 hematologic toxicity. Six patients required feeding tubes during treatment. One patient progressed locally, 8 patients progressed distantly, and none progressed regionally. Five-year locoregional progression free survival was 96%. The 3 and 5 year overall survival was 79% and 59%, respectively. Long-term complications included persistent xerostomia (n = 5), esophageal stricture requiring dilatation (n = 1), and tempromandibular joint syndrome (n = 1). CONCLUSIONS: Surgical resection followed by adjuvant chemoradiotherapy results in promising locoregional control for high-risk salivary malignancy patients.

The clinicopathologic spectrum of benign mass lesions of the vocal fold due to vocal abuse.

Benign masses of the vocal fold related to phonotrauma are clinically classified into polyps, nodules, Reinke's edema, and cysts. Despite the apparent distinctiveness of the clinical nomenclature, low inter- and intraobserver diagnostic agreement has been reported. Excepting cysts, which are epithelial lined, histologic examination of the remaining lesions has shown a variety of overlapping features insufficiently specific for the clinical diagnoses. This study reviews the clinicopathologic characteristics among these benign lesions of the vocal fold. A total of 78 nonneoplastic lesions of the vocal fold were reviewed by 2 pathologists for the presence of epithelial hyperplasia, basement membrane thickening, edema, vascular proliferation, and extracellular "amyloid-like" fibrin. In 46 cases with prebiopsy stroboscopic images, 2 otolaryngologists classified each lesion as polyp, nodule, Reinke's edema, cyst, or other. They agreed in 43% (n = 20, 13 polyps, 5 nodules, 1 Reinke's edema, 1 other) and disagreed in 57% (n = 26). There was no histologic feature that reliably distinguished among the lesions. In addition, reactive stromal cell atypia was present in 14 cases. Cysts were distinctive, as all were epithelial lined. The clinicopathologic classification of benign laryngeal lesions is neither clinically reproducible nor histologically unique. Treatment will continue to be individualized based on clinical judgment.

Prior chemoradiotherapy adversely impacts outcomes of recurrent and second primary head and neck cancer treated with concurrent chemotherapy and reirradiation.

BACKGROUND: It has been shown that concomitant chemotherapy (C) with reirradiation (ReRT) is feasible and effective for select patients with recurrent or second primary head and neck cancer (HNC). To examine potential prognostic factors associated with survival, the authors of this report retrospectively reviewed the outcomes of patients who received CReRT. METHODS: The study cohort comprised previously irradiated patients with nonmetastatic disease from 9 consecutive phase 1 and 2 protocols for poor-prognosis HNC. For all patients, reirradiation (ReRT) was delivered with concurrent chemotherapy. Chemotherapy generally was 5-fluorouracil, hydroxyurea, and a third agent. RESULTS: One hundred sixty-six patients were identified, including 81 patients who underwent surgical resection or debulking before enrollment. The median ReRT dose was 66 gray. After a median follow-up of 53 months among surviving patients, the median overall survival (OS) was 10.3 months. The 2-year rates for OS, disease-free survival, locoregional control, and freedom from distant metastasis were 24.8%, 19.9%, 50.7%, and 61.4%, respectively. Thirty-three patients (19.9%) died of treatment-related toxicity. In subgroup analysis, survival was significantly reduced in patients who received previous concurrent chemoradiotherapy (CRT) compared with patients who were naive to CRT (2-year OS rate, 10.8% vs 28.4%; P = .0043). In multivariable analysis, prior CRT was associated independently with OS along with surgery before protocol treatment, full-dose ReRT, and radiotherapy interval. CONCLUSIONS: CReRT achieved a long-term cure for a small group of patients with recurrent or second primary HNC. Previous treatment with CRT was among the important prognostic factors for survival. Because of the associated risk of severe toxicity, CReRT should be limited only to carefully selected patients.

Chemoradiation for patients with advanced oral cavity cancer.

OBJECTIVES/HYPOTHESIS: Patients with advanced oral cavity cancer (OCC) typically have not been enrolled in clinical trials utilizing contemporary multimodality strategies. There exist dogmatic expectations of inferior outcome in OCC patients secondary to ineffectiveness of treatment and unacceptable toxicity. The purpose of this study was to analyze survival, swallowing function, and incidence of osteoradionecrosis (ORN) of patients with stage III/IV OCC who have undergone primary concomitant chemoradiotherapy (CRT). METHODS: All advanced OCC patients who were enrolled in University of Chicago concomitant CRT protocols from 1994 to 2008 were reviewed. One hundred eleven newly diagnosed advanced OCC patients were evaluated. We performed a subset analysis of 27 additional advanced OCC patients who underwent surgery followed by postoperative CRT. Swallowing function was assessed via oropharyngeal motility study, and a Swallowing Performance Status Scale score was assigned. Presence of clinically significant ORN was documented. RESULTS: Median follow-up was 3.25 years. Five-year overall and progression-free survival was 66.9% and 65.9%, respectively. There was no difference in overall or progression-free survival when the surgery-first group was compared with the primary CRT group (P = .88 and P = .86 respectively). Function, without gastric tube requirement, was excellent, with 92.2% of patients able to maintain weight via oral route. Incidence of ORN was 18.4%, occurring in nine of 49 patients evaluated. CONCLUSIONS: Our data support the use of primary CRT as a viable treatment option for patients with advanced OCC. Survival is high, and overall function for the majority of patients is satisfactory. Patients with T4 oral tongue cancer may be spared total glossectomy. The incidence of ORN may be considered acceptable, in light of the benefits of enduring life and function.