scholarly journals Non-HPV-Related Head and Neck Squamous Cell Carcinoma in a Young Patient Cohort

2020 ◽  
pp. 014556132093583
Author(s):  
Michael I. Dougherty ◽  
William Dougherty ◽  
Joshua J. Kain ◽  
Brian B. Hughley ◽  
David C. Shonka ◽  
...  

Objectives: Head and neck squamous cell carcinoma (HNSCC) is rare in patients younger than 40 years. Many practitioners suspect HNSCC is a more aggressive disease in this age group, and perhaps increasing in incidence; however, there are scant and conflicting data to support this assertion. We sought to compare outcomes for young patients with non-human papillomavirus (HPV)–related HNSCC to those of older patients. Methods: A retrospective chart review of patients with HNSCC treated from 2004 to 2016 at 2 tertiary referral centers. Patients aged 18 to 40 with p16-negative HNSCC were included in the young patient cohort (n = 59). A randomly selected stage- and subsite-matched cohort aged 55 to 65 was analyzed for comparison (n = 114). Results: When considering all patients with HNSCC, patients younger than 40 were more likely to have oral tongue cancer (62.7%) compared to patients age 55 to 65 (16.9%). When an older patient cohort was stage- and subsite-matched to the young patient cohort, there were more never smokers (49.2% vs 17.5% of older patients, P < .01) and females (40.7% vs 24.6% of older patients, P = .028) in the young patient group. The young patient cohort had better average overall survival than the older group (14.4 vs 8.1 years, respectively, P = .02), but similar average disease-free survival (6.2 years vs 6.6 years, respectively, P = .67); 50.9% of young patients had tumors with adverse histologic features versus 42.0% of older patients ( P = .28). The young patients demonstrated a superior average conditional survival after recurrence (9.8 years vs 3.2 years for older patients, P < .01). Conclusions: Despite the limitations of study design, these data suggest that young patients who develop non-HPV-related HNSCC tend to have similarly aggressive disease, but longer overall survival and better survival after recurrence. These findings may be attributable to better overall health as evidenced by fewer comorbidities.

2021 ◽  
Vol 10 ◽  
Author(s):  
Yang Yang ◽  
Jaeil Ahn ◽  
Rekha Raghunathan ◽  
Bhaskar V. Kallakury ◽  
Bruce Davidson ◽  
...  

Sulfation of heparan sulfate proteoglycans (HSPG) regulates signaling of growth factor receptors via specific interactions with the sulfate groups. 6-O-Sulfation of HSPG is an impactful modification regulated by the activities of dedicated extracellular endosulfatases. Specifically, extracellular sulfatase Sulf-2 (SULF2) removes 6-O-sulfate from HS chains, modulates affinity of carrier HSPG to their ligands, and thereby influences activity of the downstream signaling pathway. In this study, we explored the effect of SULF2 expression on HSPG sulfation and its relationship to clinical outcomes of patients with head and neck squamous cell carcinoma (HNSCC). We found a significant overexpression of SULF2 in HNSCC tumor tissues which differs by tumor location and etiology. Expression of SULF2 mRNA in tumors associated with human papillomavirus (HPV) infection was two-fold lower than in tumors associated with a history of tobacco and alcohol consumption. High SULF2 mRNA expression is significantly correlated with poor progression-free interval and overall survival of patients (n = 499). Among all HS-related enzymes, SULF2 expression had the highest hazard ratio in overall survival after adjusting for clinical characteristics. SULF2 protein expression (n = 124), determined by immunohistochemical analysis, showed a similar trend. The content of 6-O-sulfated HSPG, measured by staining with the HS3A8 antibody, was higher in adjacent mucosa compared to tumor tissue but revealed no difference based on SULF2 staining. LC-MS/MS analysis showed low abundance of N-sulfation and O-sulfation in HS but no significant difference between SULF2-positive and SULF2-negative tumors. Levels of enzymes modifying 6-O-sulfation, measured by RT-qPCR in HNSCC tumor tissues, suggest that HSPG sulfation is carried out by the co-regulated activities of multiple genes. Imbalance of the HS modifying enzymes in HNSCC tumors modifies the overall sulfation pattern, but the alteration of 6-O-sulfate is likely non-uniform and occurs in specific domains of the HS chains. These findings demonstrate that SULF2 expression correlates with survival of HNSCC patients and could potentially serve as a prognostic factor or target of therapeutic interventions.


2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e18020-e18020
Author(s):  
Michelle Echevarria ◽  
Christine H. Chung ◽  
Kedar Kirtane ◽  
Jameel Muzaffar ◽  
Julie Ann Kish ◽  
...  

e18020 Background: Stereotactic body radiation therapy (SBRT) is a standard option for re-irradiation of recurrent or second primary cancers of the head and neck. We conducted performed a phase I clinical trial to establish a maximum tolerated dose of SBRT with concurrent cisplatin. We previously reported our safety data, and now present our secondary disease control endpoints. Methods: Major inclusion criteria were recurrence of previous squamous cell carcinoma of the head and neck in patients who had previously undergone radiotherapy to doses ≥ 45 Gy to the area of recurrence, ≥ 6 months prior to enrollment, and who were medically unfit for surgery, deemed unresectable, or refused surgery. Patients were treated with radiation therapy every other day for five fractions at three dose levels: 30 Gy, 35 Gy, and 40 Gy. Cisplatin was given prior to every SBRT fraction at a dose of 15 mg/m2. Secondary end points reported herein are locoregional control (LRC), freedom from distant metastasis (FFDM), and overall survival (OS). Results: Twenty patients were enrolled and of those 18 patients were evaluable for secondary endpoints. Nine patients had a primary tumor in the oropharynx, four patients in the oral cavity, three in the neck, one in the larynx, and one simultaneously in the larynx and neck. All patients received the planned dose of Cisplatin. Five patients received a radiation dose of 30 Gy, three patients received a dose of 35 Gy, and 9 patients received a dose of 40 Gy. Median gross tumor volume (GTV) was 11.725 cm3. With a median follow up of 9 months the 1-year OS was 38.9%. LRC at 1 year was 45.7% and FFDM at 1 year was 87.8%. There was a trend to improved OS with increasing SBRT dose, 40 Gy vs < 40 Gy (p = 0.08). There was an improved 1-year OS with a GTV ≤11.725 cm3 of 77.8% vs 0% for tumors > 11.725 cm3 (p < 0.001). For patients with a GTV < 11.725 cm3 who received 40 Gy the 1 year OS was 100% compared with 0% for tumors larger than 11.725 cm3. Conclusions: For patients with previously radiated locally or regionally recurrent head and neck cancer, SBRT up to 40 Gy given concurrently with cisplatin provides reasonable locoregional control and overall survival for patients with smaller tumors. Further evaluation in prospective trials is warranted. Clinical trial information: NCT02158234.


2019 ◽  
Vol 128 (10) ◽  
pp. 949-955
Author(s):  
Christopher Blake Sullivan ◽  
Nicholas S. Andresen ◽  
Nicholas Kendell ◽  
Zaid Al-Qurayshi ◽  
Nitin A. Pagedar

Objectives: Survival outcomes for advanced non-melanoma skin cancers of the head and neck treated with surgical resection are not well described in the literature. We aimed to describe outcomes for T3 and T4 cutaneoous squamous cell carcinoma of the head or neck treated with surgical resection at 1 tertiary academic medical center. Methods: We analyzed a retrospective cohort of patients diagnosed with T3 or T4 cutaneous squamous cell carcinoma (SCC) of the head or neck from 2005 to 2016 treated with definitive surgical resection. Survival outcomes were examined using Kaplan-Meier analysis, and multivariate analysis was completed with Cox proportional hazard model. Results: Forty-three patients met inclusion criteria. The mean age at diagnosis was 74.7 years (SD = 10.2), and 34 (79.1%) patients were male. Twelve (27.9%) patients were immunosuppressed. Radical resection, defined as temporal bone resection, orbital exenteration, calvarial resection, mandibulectomy, or maxillectomy, was performed in 25 (58.1%) cases. Final surgical margins were positive in 19 (44.2%) cases. Patients with tumors of the scalp/neck had a 1-year survival probability of 85.7%, and the probability of survival 1 year after a neck dissection was greater than 93%. Conclusion: Anatomical subsites, specifically scalp/neck tumors, tended to have worse overall survival. Positive final margins tended to indicate a worse prognosis, and overall survival and recurrence were not significantly different among patients who underwent radical surgical resection compared to soft tissue resection.


2017 ◽  
Vol 35 (15_suppl) ◽  
pp. 6035-6035
Author(s):  
Sujith Baliga ◽  
Rafi Kabarriti ◽  
Nitin Ohri ◽  
Chandan Guha ◽  
Shalom Kalnicki ◽  
...  

6035 Background: The role of radiation therapy (RT) in the upfront management of patients with metastatic head and neck squamous cell carcinoma (HNSCC) is not clearly defined. In this study, we used the National Cancer Database (NCDB) to assess the association between RT use and overall survival (OS) for patients with metastatic HNSCC who received chemotherapy. Methods: We analyzed the NCDB to identify patients with newly diagnosed metastatic HNSCC from 2004-2013 who were treated with upfront chemotherapy. Associations between the use of RT and OS were evaluated using the Kaplan Meier method, univariate and multivariate cox regression, propensity score matching, and sequential landmark analysis. Survival outcomes were also compared for patients receiving a biologically effective dose (BED) ≥72 Gy10 and < 72 Gy10. Results: We identified 3,516 patients diagnosed with metastatic HNSCC who were treated with chemotherapy, of which 2,288 (65%) were also treated with RT. The median follow up was 11.9 months. The addition of RT to chemotherapy was associated with prolonged survival (median 13.6 v 11.3 months, logrank p < 0.001). On multivariate analysis, the use of RT remained associated with prolonged survival (HR = 0.71, 95% CI 0.61-0.82, p < 0.001). After propensity score matching, the addition of RT was associated with improved median survival (13.5 v 11.2 months) and 5-year (17% v 7%) OS compared to chemotherapy alone (log rank, p < 0·001). Landmark analyses limited to patients who survived at least 3, 6, and 12 months after diagnosis continued to demonstrate improved OS with the addition of RT. Among patients treated with RT, the use of RT schedules with a BED exceeding 72 Gy10 was associated with prolonged survival (median 18.0 versus 11.7 months, logrank p < 0.001). Conclusions: For patients with metastatic HNSCC, the addition of RT to chemotherapy was associated with improved OS in this population based study. These results provide rationale for prospective randomized trials to validate these findings and to determine the optimal radiation therapy dose/fractionation and treatment schedule for these patients.


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