Association of serum level of YKL-40 in patients with squamous cell carcinoma of the head and neck with survival

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 5551-5551
Author(s):  
A. Roslind ◽  
J. S. Johansen ◽  
I. J. Christensen ◽  
J. Bentzen ◽  
D. L. Nielsen ◽  
...  

5551 Background: High serum YKL-40 is associated with poor prognosis in breast-, colorectal-, ovarian-, prostate-, small cell lung carcinoma and malignant melanoma. YKL-40 is secreted by cancer cells, macrophages and neutrophils. Its function in cancer is unknown. It may be a growth factor, play a role in angiogenesis or protect against apoptosis. The aim was to examine serum YKL-40 in patients with squamous cell carcinoma of the head and neck (SCCHN). Methods: YKL-40 was determined by ELISA (Quidel, Santa Clara, CA) in serum samples from 138 patients with SCCHN (median age 60, range 44–92 years) before surgery and/or fractionated radiotherapy (total dose of 60–68 Gy, 2-Gy fractions). 42 patients had stage 1, 28 stage 2, 22 stage 3, and 46 stage 4 disease. The median follow-up time was 4.0 years (range 15 days–8.5 years). 91 patients had died. Results: Serum YKL-40 was increased (p < 0.001) in patients with SCCHN (median 120 μg/l, range 25–1848 μg/l) compared to healthy controls (43 μg/l, 20–184 μg/l, n = 245). Serum YKL-40 was elevated in 52% of the patients. Patients with stage 1 disease had lower, but non-significant, serum YKL-40 compared to patients with stage 2–4 disease (median 113 μg/l, range 25–1000 μg/l vs. 139 μg/l, 29–1848 μg/l, p = 0.06). Patients with high serum YKL-40 had significantly shorter survival than patients with normal serum YKL-40 (33 months vs. 74 months, p = 0.01 logrank test). Univariate analysis of serum YKL-40 (log transformed and treated as a continuous covariate) showed significant association with overall survival after start of therapy (HR = 1.4, 95% CI: 1.2–1.7, p = 0.0004). Multivariate Cox analysis including age, stage and serum YKL-40 (log transformed and treated as a continuous variable) showed that stage (stage 3–4 vs. stage 1–2, HR = 3.0, 95% CI: 1.9–4.6, p < 0.0001) and serum YKL-40 (HR = 1.5, 95% CI: 1.2–1.8, p = 0.0003) were independent prognostic variables of overall survival. Conclusions: Serum YKL-40 is a prognostic biomarker of overall survival in SCCHN patients. No significant financial relationships to disclose.

2020 ◽  
pp. 000348942097777
Author(s):  
Katie M. Mingo ◽  
Adeeb Derakhshan ◽  
Neelab Abdullah ◽  
Deborah J. Chute ◽  
Shlomo A. Koyfman ◽  
...  

Objectives: To analyze characteristics, treatment outcomes, and prognostic factors of sarcomatoid squamous cell carcinoma of the head and neck. Study Design: Retrospective chart review. Setting: Tertiary care center. Subjects and Methods: Fifty-five patients were treated for sarcomatoid squamous cell carcinoma of the head and neck between 1996 and 2018. Data collection included clinical history, tumor characteristics, pathology, treatment modality, and outcomes. Mean follow up was 17.1 months. Cox univariate analysis was used to evaluate for associations with locoregional recurrence, distant metastasis, and overall survival. Results: Most patients were white males with a smoking history and median age 66 years (range 41-92) at diagnosis. Twenty-two percent had prior head and neck radiation. Tumor site was most frequently oral cavity (41.8%), followed by larynx (29.1%), and oropharynx (16.4%). Half presented with early T stage disease (15.5% T0, 12.7% T1, 30.9% T2) and the remainder with late stage disease (16.4% T3, 34.5% T4). Locoregional recurrence rate was 60.0%, metastatic recurrence was rate 21.8%, with median time to recurrence of 4 months and mean overall survival of 20 months. Presence of lymphovascular space invasion was statistically associated with locoregional recurrence ( P = .018, HR 3.55 [95% CI 1.24, 10.14]) and poorer overall survival ( P = .015, HR 2.92 [95% CI 1.23, 4.80]). Treatment with multimodality therapy was associated with decreased locoregional recurrence ( P = .039, HR 0.39 [95% CI 0.16, 0.95]) but did not impact overall survival. Conclusion: Sarcomatoid squamous cell carcinoma remains a rare and aggressive disease variant with high recurrence rates and high mortality. High risk features such as lymphovascular space may indicate the need for more aggressive therapy.


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.


2002 ◽  
Vol 20 (18) ◽  
pp. 3850-3856 ◽  
Author(s):  
Mauro Piantelli ◽  
Stefano Iacobelli ◽  
Giovanni Almadori ◽  
Manuela Iezzi ◽  
Nicola Tinari ◽  
...  

PURPOSE: Galectin-3 is a pleiotropic carbohydrate-binding protein participating in a variety of normal and pathologic processes, including cancer progression. This study was aimed at evaluating the prognostic value of galectin-3 expression in node-negative laryngeal squamous-cell carcinoma (SCC). PATIENTS AND METHODS: Galectin-3 expression was analyzed by immunohistochemistry using M3/38 monoclonal antibody, in a single-institution series of 73 node-negative laryngeal SCC patients (median follow-up, 52 months; range, 2 to 90 months). RESULTS: Forty-two (57.5%) of 73 patients expressed galectin-3. Galectin-3 expression was positively associated with tumor keratinization and histologic grade. A significant correlation was found between galectin-3 tumor positivity and longer relapse-free and overall survival. In univariate analysis, high-grade (grade 3 or 4) tumors, nonkeratinizing tumors, and galectin-3–negative tumors showed a significantly increased risk of relapse and death. In multivariate analysis, only galectin-3 expression retained an independent prognostic significance for both relapse-free and overall survival. CONCLUSION: We conclude that the absence of galectin-3 expression is an independent negative prognostic marker in laryngeal SCC patients. Thus, histochemical detection of galectin-3 in these tumors could be useful for the selection of node-negative patients with potentially unfavorable outcomes, to establish adjuvant therapy protocols.


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.


2004 ◽  
Vol 22 (19) ◽  
pp. 3965-3972 ◽  
Author(s):  
Volkert B. Wreesmann ◽  
Weiji Shi ◽  
Howard T. Thaler ◽  
Ashok Poluri ◽  
Dennis H. Kraus ◽  
...  

Purpose The goal of this study was to identify chromosomal aberrations associated with poor outcome in patients with head and neck squamous cell carcinoma (HNSCC). Patients and Methods We assessed the global genomic composition of 82 HNSCCs from previously untreated patients with comparative genomic hybridization (CGH). The CGH data were subcategorized into individual cytogenetic bands. Only genomic aberrations occurring in more than 5% of cases were analyzed, and redundancies were eliminated. Each aberration was submitted to univariate analysis to assess its relationship with disease-specific survival (DSS). We used Monte Carlo simulations (MCS) to adjust P values for the log-rank approximate χ2 statistics for each abnormality and further applied the Hochberg-Benjamini procedure to adjust the P values for multiple testing of the large number of abnormalities. We then submitted abnormalities whose univariate tests resulted in an adjusted P value of less than .15 together with significant demographic/clinical variables to stepwise Cox proportional hazards regression. We again verified and adjusted P values for the χ2 approximation of the final model by MCS. Results CGH analysis revealed a recurrent pattern of chromosomal aberrations typical for HNSCC. Univariate analysis revealed 38 abnormalities that were correlated with DSS. After controlling for multiple comparisons and confounding effects of stage, five chromosomal aberrations were significantly associated with outcome, including amplification at 11q13, gain of 12q24, and losses at 5q11, 6q14, and 21q11 (MCS adjusted P = .0009 to P = .01). Conclusion HNSCC contains a complex pattern of chromosomal aberrations. A sequential approach to control for multiple comparisons and effect of confounding variables allows the identification of clinically relevant aberrations. The significance of each individual abnormality merits further consideration.


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