Gamez, Mauricio E.

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.

Introduction: Esthesioneuroblastoma (ENB) is a rare malignant neoplasm arising from the olfactory epithelium of the cribriform plate. Although survival is excellent with a reported 5-year overall survival (OS) of 82%, recurrence is frequent and occurs in 40–50% of cases. This study investigates the characteristics of ENB recurrence and the subsequent prognosis of patients with recurrence. Methods: The clinical records of all patients diagnosed as having ENB with subsequent recurrence at a tertiary hospital from 1 January 1960 to 1 January 2020 were retrospectively reviewed. Overall survival (OS) and progression-free survival (PFS) were reported. Results: A total of 64 out of 143 ENB patients had recurrences. In total, 45 out of 64 recurrences met the inclusion criteria and were included in this study. From these, 10 (22%) had a sinonasal recurrence, 14 (31%) had an intracranial recurrence, 15 (33%) had a regional recurrence, and 6 (13%) had a distal recurrence. The average interval from initial treatment to recurrence was 4.74 years. There were no differences in rates of recurrence with respect to age, sex, or types of surgery (endoscopic, transcranial, lateral rhinotomy, and combined). The time to recurrence was shorter for Hyams grades 3 and 4 compared to Hyams grades 1 and 2 (3.75 years vs. 5.70 years, p < 0.05). Patients with recurrence limited to the sinonasal region had a lower overall primary Kadish stage compared to recurrences beyond the sinonasal region (2.60 vs. 3.03, p < 0.05). A total of 9 (20%) out of 45 patients developed secondary recurrence. Following recurrence, the subsequent 5-year OS and PFS were 63 and 56%, respectively. The mean time to secondary recurrence after treatment of the primary recurrence was 32 months, which was significantly shorter than the time to primary recurrence (32 months vs. 57 months, p = 0.048). The mean age of the secondary recurrence group is significantly older than the primary recurrence group (59.78 years vs. 50.31 years, p = 0.02). No statistically significant differences were observed between the secondary recurrence group and the recurrence group in terms of their overall Kadish stages or Hyams grades. Conclusions: Following an ENB recurrence, salvage therapy appears to be an effective therapeutic option with a subsequent 5-year OS of 63%. However, subsequent recurrences are not infrequent and may require additional therapy.

Abstract Patients with human papillomavirus‐associated oropharyngeal squamous cell carcinoma (HPV‐OPSCC) have a favorable prognosis and excellent overall survival (OS), and studies have demonstrated these findings in cohorts of predominantly White patients. Racial/ethnic (R/E) minorities, particularly Black patients, with head and neck squamous cell carcinoma (HNSCC) have worse survival outcomes compared with White patients. In this study, we aimed to determine if Black patients with HPV‐OPSCC have a similar favorable prognosis to the White population. This was a population‐based retrospective cohort study that analyzed HNSCC patients using the National Cancer Database from 2010 to 2016. We identified patients with Stage I–IV HPV‐ OPSCC who were treated with radiation, surgery, chemotherapy, or a combination of modalities. Patient outcomes were stratified by R/E groups including White Versus Black patients. The main outcome in this study was OS. Analyses for proportions of categorical variables were performed using a χ 2 or Fisher's exact test. Univariate and multivariate time‐to‐event survival analyses were performed using Kaplan–Meier product limit estimates and log‐rank test to test the differences between strata. A Cox proportional hazards regression model was used to assess the association between covariates and risk of death (OS). We identified 9256 OPSCC patients who met inclusion criteria and were treated between 2010 and 2016, of which 7912 were White (85.5%) and 1344 were Black (14.5%). A total of 1727 were HPV‐OPSCC, of which 1598 were White (92.5%) and 129 (7.5%) were Black. By race, the 5‐year OS for White versus Black OPSCC patients was 42% versus 23%, respectively (log‐rank, p < 0.0001). Among HPV‐positive OPSCC patients, the 5‐year OS for White versus Black patients was 65% versus 39% (log‐rank, p < 0.0001). Among HPV‐negative patients, the 5‐year OS for White versus Black patients was 36% versus 13% (log‐rank, p < 0.0001). On multivariate analysis, after accounting for age, sex, insurance status, income, Charlson–Deyo score, receipt of surgery, distance from facility, and total treatment time, Black race trended toward, but was not associated with worse survival. Hazard ratio (HR:1.24, 95% confidence interval [CI] 0.85–1.81, p = 0.255). This national cohort study of OPSCC patients demonstrates that Black patients with HPV‐OPSCC have a poor prognosis and OS similar to HPV‐negative White patients. This may be partly due to socioeconomic barriers such as insurance and income. Further work is needed to better understand the specific drivers of inferior survival outcomes in this specific patient population.

Purpose/Objective(s): Microbiome has been shown to affect tumorigenesis by promoting inflammation. However, the association between the upper aerodigestive microbiome and head and neck squamous cell carcinoma (HNSCC) is not well established. Hypoxia is a modifiable factor associated with poor radiation response. Our study analyzed the HNSCC tumor samples from The Cancer Genome Atlas (TCGA) to investigate the relationship between different HNSCC tumor subsites, hypoxia, and local tumor microbiome composition. Results: A total of 357 patients were included [Oral cavity (OC) = 226, Oropharynx (OPx) = 53, and Larynx/Hypopharynx (LHPx) = 78], of which 12.8%, 71.7%, and 10.3%, respectively, were HPV positive. The mean (SD) hypoxia scores were 30.18 (11.10), 24.31 (14.13), and 29.53 (12.61) in OC, OPx, and LHPx tumors, respectively, with higher values indicating greater hypoxia. The hypoxia score was significantly higher for OC tumors compared to OPx (p = 0.044) and LHPx (p = 0.002). There was no significant correlation between hypoxia and HPV status. Pseudomonas sp. in OC, Actinomyces sp. and Sulfurimonas sp. in OPx, and Filifactor, Pseudomonas and Actinomyces sp. in LHPx had the strongest association with the hypoxia score. Materials/Methods: Tumor RNAseq samples from TCGA were processed, and the R package “tmesig” was used to calculate gene expression signature, including the Buffa hypoxia (BH) score, a validated hypoxia signature using 52 hypoxia-regulated genes. Microbe relative abundances were modeled with primary tumor location and a high vs. low tertile BH score applying a gamma-distributed generalized linear regression using the “stats” package in R, with adjusted p-value < 0.05 considered significant. Conclusions: In our study, oral cavity tumors were found to be more hypoxic compared to other head and neck subsites, which could potentially contribute to their radiation resistance. For each subsite, distinct microbial populations were over-represented in hypoxic tumors in a subsite-specific manner. Further studies focusing on an association between microbiome, hypoxia, and patient outcomes are warranted.

AbstractBackgroundWe seek to inform radiotherapy (RT) delivery for adenoid cystic carcinoma of the head and neck (ACC) by evaluating RT techniques and recurrence patterns.MethodsWe identified patients with ACC treated with curative‐intent RT from 2005 to 2021. Imaging was reviewed to determine local recurrence (LR).ResultsNinety‐one patients were included. The 5‐year LR risk was 12.2% (6.6–22.7). One patient each experienced a marginal and out‐of‐field recurrence. Patients receiving >60 Gy postoperatively had a 5‐year LR risk of 0% compared to 10.7% (4.2–27.2) with ≤60 Gy. Those receiving 70 and <70 Gy definitively had a 5‐year LR risk of 15.2% (2.5–91.6) and 33.3% (6.7–100.0), respectively. No patients had regional nodal failure.ConclusionsModern, conformal RT for ACC results in low rates of LR. Doses >60 and 70 Gy may improve control in the postoperative and definitive settings, respectively. Elective nodal treatment can be omitted in well‐selected patients.

This cohort study characterizes the inclusion of Hispanic ethnicity or ethnoracial categories in breast cancer studies from the National Cancer Database.

PurposeDespite the intra- and intertumoral heterogeneity seen in glioblastoma multiforme (GBM), there is little definitive data on the underlying cause of the differences in patient survivals. Serial imaging assessment of tumor growth allows quantification of tumor growth kinetics (TGK) measured in terms of changes in the velocity of radial expansion seen on imaging. Because a systematic study of this entire TGK phenotype—growth before treatment and during each treatment to recurrence —has never been coordinately studied in GBMs, we sought to identify whether patients cluster into discrete groups on the basis of their TGK.Patients and MethodsFrom our multi-institutional database, we identified 48 patients who underwent maximally safe resection followed by radiotherapy with imaging follow-up through the time of recurrence. The patients were then clustered into two groups through a k-means algorithm taking as input only the TGK before and during treatment.ResultsThere was a significant survival difference between the clusters ( P = .003). Paradoxically, patients among the long-lived cluster had significantly larger tumors at diagnosis ( P = .027) and faster growth before treatment ( P = .003) but demonstrated a better response to adjuvant chemotherapy ( P = .048). A predictive model was built to identify which cluster patients would likely fall into on the basis of information that would be available to clinicians immediately after radiotherapy (accuracy, 90.3%).ConclusionDichotomizing the heterogeneity of GBMs into two populations—one faster growing yet more responsive with increased survival and one slower growing yet less responsive with shorter survival—suggests that many patients who receive standard-of-care treatments may get better benefit from select alternative treatments.

Objectives/HypothesisSarcomatoid carcinoma is a rare variant of squamous cell carcinoma of the head and neck. No consensus exists on its management. Our aim was to present our outcomes.Study DesignRetrospective study. Median follow‐up 45 months.MethodsThere were 38 patients with pathologically confirmed sarcomatoid carcinoma of the larynx treated at the Mayo Clinic from 1990 to 2014. Statistical analysis of overall survival (OS), progression‐free survival (PFS), and local control (LC) were conducted using the Kaplan‐Meier method.ResultsThe majority of patients were elderly males (92%) with a smoking history (74%) presenting with early‐stage disease (71%). Surgery alone was the primary treatment in 27 patients (71%). Nine patients (25%) were treated with adjuvant radiation due to initial stage or high‐risk pathologic features. Median radiation dose to the primary/surgical bed was 65 Gy (range, 60.3–75.0 Gy). A total of 15 patients (39%) had tumor recurrence, majority being local (n = 12). Sixty percent (n = 9) had multiple local recurrences. Five‐year OS, PFS, and LC were 63%, 46%, and 72%, respectively. Subgroup analysis by stage I versus higher stages (II–IV) showed an OS of 80% versus 43% (P = .030), PFS of 65% versus 18% (P = .003), and LC of 84% versus 57% (P = .039).ConclusionsSarcomatoid carcinoma of the larynx is rare, and frequently presents at an early stage in older men with history of smoking. Based on our outcomes and patterns of failure, it appears early‐stage tumors are treated appropriately with single‐modality therapy, whereas more advanced tumors require multimodality therapy. Validation in a larger cohort is warranted.Level of Evidence4. Laryngoscope, 128:373–377, 2018