Faculty Bibliography

IMPORTANCE:The long-term outcomes associated with adding bevacizumab, a vascular endothelial growth factor inhibitor, to standard chemoradiation have continued to be favorable for a group of patients with locoregionally advanced nasopharyngeal carcinoma (NPC). OBJECTIVE:To assess long-term toxic effects and clinical outcomes associated with chemotherapy, radiation therapy (RT), and bevacizumab for NPC. DESIGN, SETTING, AND PARTICIPANTS:This single-arm phase II nonrandomized controlled trial was conducted by the National Cancer Trials Network group and NRG Oncology (formerly Radiation Therapy Oncology Group), with accrual from December 13, 2006, to February 5, 2009, and data analysis from June 26 to July 1, 2019. The study was conducted at 19 cancer centers with a median (IQR) follow-up of 9.0 (7.7-9.3) years. Included patients were adults (aged ≥18 years) with NPC that was World Health Organization (WHO) histologic grade I to IIb or III, American Joint Committee on Cancer stage IIB or greater, and with or without lymph node involvement. INTERVENTIONS:Patients received 3 cycles of bevacizumab (15 mg/kg) concurrently with standard cisplatin (100 mg/m2) and RT (69.96 Gy) followed by 3 cycles of adjuvant bevacizumab (15 mg/kg) given concurrently with cisplatin (80 mg/m2) and fluorouracil (1000 mg/m2/d). MAIN OUTCOMES AND MEASURES:The primary end point was grade 4 hemorrhage or grade 5 adverse events in the first year. Secondary end points were locoregional progression-free (LRPF) interval, distant metastasis-free (DMF) interval, progression-free survival (PFS), overall survival (OS), and other adverse events. Long-term toxic effects and clinical outcomes were reported due to the limited follow-up in the initial report for this trial and the importance of long-term outcomes when combining bevacizumab with chemoradiation. RESULTS:Among 46 patients with NPC who were enrolled, 44 patients were analyzed (29 males [65.9%]; 23 Asian [52.3%], 2 Black [4.5%], and 16 White [36.4%]; 38 not Hispanic [86.4%]; median [IQR] age, 48.5 [39.0-56.0] years). There were 33 patients with a Zubrod performance status of 0, indicating that they were fully functional and asymptomatic (75.0%); 32 patients with a WHO histologic grade of IIb or III (72.7%); and 39 patients with stage III or IVB disease (88.6%). Among analyzed patients, 42 individuals received radiation therapy of 69.96 Gy or greater (95.5%; dose range, 65.72-70.00 Gy); 30 patients received 3 cycles of cisplatin (68.2%) with RT, and 31 patients received 3 cycles of bevacizumab with RT (70.5%); this was followed by 3 cycles of adjuvant cisplatin in 21 patients (47.7%), fluorouracil in 24 patients (54.5%), and bevacizumab in 23 patients (52.3%). No grade 4 hemorrhage or grade 5 AEs were reported in the first year or thereafter. Late grade 3 AEs occurred in 16 patients (36.4%), including 7 patients with dysphagia (15.9%), 6 patients with hearing impairment (13.6%), and 2 patients with dry mouth (4.5%). The 1- and 5-year rates of feeding tube use were 5 of 41 patients (12.2%) and 0 of 27 patients, respectively. There were 19 patients (43.2%) who progressed or died without disease progression (6 patients with locoregional progression [13.6%], 8 patients with distant progression [18.2%], and 5 patients who died without progression [11.4%]). The 5- and 7-year rates were 79.5% (95% CI, 67.6%-91.5%) and 69.7% (95% CI, 55.9%-83.5%) for OS, 61.2% (95% CI, 46.8%-75.6%) and 56.3% (95% CI, 41.5%-71.1%) for PFS, 74.9% (95% CI, 61.4%-86.6%) and 72.3% (95% CI, 58.4%-84.7%) for LRPF interval, and 79.5% (95% CI,66.4%-90.0%) for both times for DMF interval. Among 13 patients who died, death was due to disease in 8 patients (61.5%). CONCLUSIONS AND RELEVANCE:In this nonrandomized controlled trial, no grade 4 hemorrhage or grade 5 AEs were reported in the first year or thereafter among patients with NPC receiving bevacizumab combined with chemoradiation. The rate of distant metastasis was low although 89% of patients had stage III to IVB disease, suggesting that further investigation may be warranted. TRIAL REGISTRATION:ClinicalTrials.gov Identifier: NCT00408694.

Background: Racial/ethnic (R/E) minorities with head and neck squamous cell carcinoma (HNSCC) have worse survival outcomes compared to White patients. While disparities in patient outcomes for R/E minorities have been well documented, the specific drivers of the inferior outcomes remain poorly understood. Patients and Methods: This was a population-based retrospective cohort study that analyzed HNSCC patients using the National Cancer Database (NCDB) from 2000"“2016. Patient outcomes were stratified by R/E groups including White, Black, Hispanic, Native American/Other, and Asian. The main outcome in this study was overall survival (OS). Univariate time-to-event survival analyses were performed using the Kaplan"“Meier product limit estimates and the log-rank test to evaluate the differences between strata. Results: There were 304,138 patients with HNSCC identified in this study, of which 262,762 (86.3%) were White, 32,528 (10.6%) were Black, 6191 were Asian (2.0%), and 2657 were Native American/Other (0.9%). Black R/E minorities were more likely to be uninsured (9% vs. 5%, p < 0.0001), have Medicaid insurance (22% vs. 8%, p < 0.0001), be in a lower income quartile (<30,000, 42% vs. 13%, p < 0.0001), have metastatic disease (5% vs. 2%, p < 0.001), and have a total treatment time 6 days longer than White patients (median 107 vs. 101 days, p < 0.001). The 5-year OS for White, Black, Native American/Other, and Asian patients was 50.8%, 38.6%, 51.1%, and 55.8%, respectively. Among the oropharynx HNSCC patients, the 5-year OS rates in p16+ White, Black, and Asian patients were 65.7%, 39.4%%, and 55%, respectively. After a multivariate analysis, Black race was still associated with an inferior OS (HR:1.09, 95% CI: 1.03"“1.15, p = 0.002). Conclusions: This large cohort study of HNSCC patients demonstrates that Black race is independently associated with worse OS, in part due to socioeconomic, clinical, and treatment-related factors.

BACKGROUND:The present study characterizes national trends in the utilization of adjuvant chemotherapy to treat salivary gland malignancies. METHODS:The National Cancer Database was queried for salivary gland malignancies treated by surgery with radiation in 2004-2019. Proportions of patients receiving adjuvant chemotherapy over the study period were analyzed by linear regression. The impact of chemotherapy on overall survival was assessed using Kaplan-Meier and Cox proportional hazards analyses. RESULTS:Among 15 965 patients meeting inclusion criteria, 2355 (14.8%) received adjuvant chemotherapy. Chemotherapy utilization significantly increased from 4.9% to 16.5% over the study period (p < 0.001). No survival benefit was observed with adjuvant chemotherapy on propensity score-matched Kaplan-Meier analysis (HR: 0.98; 95% CI: 0.86-1.11; p = 0.72) or multivariable Cox regression (HR: 0.92; 95% CI: 0.78-1.09; p = 0.34). CONCLUSIONS:Adjuvant chemotherapy has been increasingly utilized to treat salivary gland malignancies in recent years. Our findings highlight the importance of obtaining high-quality prospective data regarding the benefit of chemotherapy.

PURPOSE/OBJECTIVE:Locoregionally recurrent head and neck cancer is a complex clinical scenario that often requires multimodality treatment. These patients have often previously received definitive treatment with a combination of surgery, radiation therapy, and systemic therapy, which can make further management difficult. A second isolated locoregional failure is rare and clinicians are faced with a challenge to optimize disease control while minimizing treatment-related toxicity. METHODS AND MATERIALS/METHODS:In this report, we present the diagnosis, management, and outcomes of a patient with an isolated locoregional recurrence who was previously treated with two courses of radiation. The patient was treated with a second course of reirradiation using interstitial brachytherapy as well as a discussion regarding patient selection and optimal management for recurrent head and neck cancer. RESULTS:Repeat reirradiation using interstitial HDR-brachytherapy with the use of an alloderm spacer was successfully delivered to the patient for an in-field right neck nodal recurrence. He received a total EQD2/BED dose of 127.70/153.24 Gy. At 1-year followup, the patient was without evidence of recurrent disease or new significant side effects. CONCLUSION/CONCLUSIONS:Recurrent head and neck cancer should be managed with a multidisciplinary approach given the complex clinical scenario. Reirradiation is a commonly used salvage measure for recurrent head and neck cancer that requires careful planning and patient selection due to prior treatment-related effects and dose constraints. We reported a case of a second course of reirradiation using interstitial HDR-brachytherapy for locoregionally recurrent head and neck cancer and showed no recurrence of disease or worsening long term side effects at 1 year.

Purpose/Objective(s): HNSCS is a rare diagnosis with an overall poor prognosis. Due to its rarity, our understanding of HNSCS and its optimal management is mainly derived from retrospective and single-institution studies. We aimed to evaluate the disease characteristics, patterns of care, and survival outcomes in patients with HNSCS. Materials/Methods: Using the National Cancer Database (NC

BACKGROUND:Computerized surgical planning (CSP) in osseous reconstruction of head and neck cancer defects has become a mainstay of treatment. However, the consequences of CSP-designed titanium plating systems on planning adjuvant radiation remains unclear. METHODS:Two patients underwent head and neck cancer resection and maxillomandibular free fibula flap reconstruction with CSP-designed plates and immediate placement of osseointegrated dental implants. Surgical treatment was followed by adjuvant intensity modulated radiation therapy (IMRT). RESULTS:Both patients developed osteoradionecrosis (ORN), and one patient had local recurrence. The locations of disease occurred at the areas of highest titanium plate burden, possibly attributed to IMRT dosing inaccuracy caused by the CSP-designed plating system. CONCLUSION/CONCLUSIONS:Despite proven benefits of CSP-designed plates in osseous free flap reconstruction, there may be an underreported risk to adjuvant IMRT treatment planning leading to ORN and/or local recurrence. Future study should investigate alternative plating methods and materials to mitigate this debilitating outcome.

OBJECTIVES/HYPOTHESIS/OBJECTIVE:Non-squamous cell carcinoma (SCC) malignancies are rare, but well described laryngeal pathologies. However, the epidemiology and clinical behavior of these tumors is not well studied. STUDY DESIGN/METHODS:Retrospective cohort study. METHODS:Patients diagnosed with non-squamous cell larynx cancer from 2004 to 2017 in the National Cancer Database were selected. Demographic, clinicopathologic factors, treatments, and survival were analyzed. Univariable and multivariable cox regression were performed. Survival was compared with a propensity score-matched (PSM) population of laryngeal SCC patients. RESULTS:A total of 136,235 cases of larynx cancer were identified. After excluding SCC variants, 2,172 (1.6%) patients met inclusion criteria. The most common histology was chondrosarcoma (374, 17.2%), followed by small cell (345, 15.9%), and spindle cell carcinoma (268, 12.3%). The most common treatment was surgery (683, 31.4%) followed by chemoradiation (409, 18.8%) and surgery and adjuvant radiation (288, 13.3%). Overall, 3- and 5-year survival was 67.9% and 59.4%, respectively. In multivariate analysis controlling for age, stage, comorbidity, histology, and treatment modality; chondrosarcoma had the best survival (hazard ratio [HR] 0.11, confidence interval [CI] 0.07-0.19, P < .001). In a PSM population, matched for age, stage, comorbidity, and treatments; non-SCC patients had significantly lower survival (51.5% vs. 59.9%, P < .001). CONCLUSION/CONCLUSIONS:A diverse range of non-squamous cell malignancies occur in the larynx. In general, these tumors have poor survival, with few exceptions such as chondrosarcoma. While the majority of these histologies undergo surgical-based treatments in other sites, only 53% of patients underwent surgical-based treatment in the larynx. These data could guide clinicians in determining the outcome of treatment in these patients. LEVEL OF EVIDENCE/METHODS:4 Laryngoscope, 2022.

OBJECTIVE:Carcinosarcoma of the salivary gland is a rare malignant biphasic tumor. The present study investigates the epidemiology and clinical behavior of carcinosarcoma of the major salivary glands using the National Cancer Database (NCDB). STUDY DESIGN/METHODS:Historical cohort study. SETTING/METHODS:NCDB. METHODS:All tumors were selected between 2004 and 2018. Patient demographics, tumor characteristics, treatments, and survival were analyzed. Cox regression analysis was performed in surgically treated patients. RESULTS:= .008) remained significant. CONCLUSION/CONCLUSIONS:Carcinosarcoma is a rare salivary gland tumor that frequently presents at a locally advanced stage. Despite multimodality treatments, the outcomes are poor. In the absence of clinical trial data, these data from the NCDB could guide clinicians in the management of this rare disease.