Characteristics and Outcomes in Head and Neck Sarcomatoid Squamous Cell Carcinoma: The Cleveland Clinic Experience

2020 ◽  
pp. 000348942097777
Author(s):  
Katie M. Mingo ◽  
Adeeb Derakhshan ◽  
Neelab Abdullah ◽  
Deborah J. Chute ◽  
Shlomo A. Koyfman ◽  
...  
Keyword(s):  
Overall Survival ◽  
Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Head And Neck ◽  
Squamous Cell ◽  
Locoregional Recurrence ◽  
Univariate Analysis ◽  
Tertiary Care ◽  
Smoking History ◽  
Stage Disease

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.

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 ◽  
...  
Keyword(s):  
Overall Survival ◽  
Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Head And Neck ◽  
Squamous Cell ◽  
Small Cell Lung Carcinoma ◽  
Univariate Analysis ◽  
High Serum ◽  
Cell Lung Carcinoma ◽  
Stage 1

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.

scholarly journals Expression of the Extracellular Sulfatase SULF2 Affects Survival of Head and Neck Squamous Cell Carcinoma Patients

2021 ◽  
Vol 10 ◽  
Author(s):  
Yang Yang ◽  
Jaeil Ahn ◽  
Rekha Raghunathan ◽  
Bhaskar V. Kallakury ◽  
Bruce Davidson ◽  
...  
Keyword(s):  
Overall Survival ◽  
Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Head And Neck ◽  
Squamous Cell ◽  
Hpv Infection ◽  
Neck Squamous Cell Carcinoma ◽  
Therapeutic Interventions ◽  
Tumor Tissues ◽  
Significant Difference

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.

scholarly journals Outcomes of Sinonasal Squamous Cell Carcinoma with and without Association of Inverted Papilloma: A Multi-Institutional Analysis

2017 ◽  
Vol 31 (5) ◽  
pp. 305-309 ◽  
Author(s):  
Brian C. Lobo ◽  
Brian D'Anza ◽  
Janice L. Farlow ◽  
Dennis Tang ◽  
Troy D. Woodard ◽  
...  
Keyword(s):  
Overall Survival ◽  
Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Cleveland Clinic ◽  
Nodal Metastasis ◽  
Inverted Papilloma ◽  
Low Grade ◽  
Primary Tumors ◽  
Stage Disease

Introduction Sinonasal squamous cell carcinoma (SCC) accounts for <1% of all malignancies but represents 70% of sinonasal cancer. Up to 10% of SCCs are associated with inverted papilloma (IPSCC). Studies that compare patients, treatment, and outcomes of SCC and IPSCC are absent in the literature. Methods A retrospective review of patients with SCC and those with IPSCC at Cleveland Clinic and Indiana University from 1995 to 2015. The records were analyzed for demographics, tumor characteristics, treatment, and outcomes. Results The study comprised 117 patients with SCC, of whom, 29 had IPSCC. The mean age at diagnosis was similar: 63 and 64 years for patients with SCC and patients with IPSCC, respectively; with female patients representing 36% and 34%, respectively (p > 0.99). Smokers represented 64% of the patients with SCC and 55% of patients with IPSCC (p = 0.3); excessive alcohol intake was noted in 16% of the patients with SCC and 21% of the patients with IPSCC (p = 0.56). The maxillary sinus was most commonly involved, followed by the nasal cavity (51% versus 35% SCC, 45% versus 38% IPSCC). Frontal ethmoid and sphenoid sinuses contained primary tumors only in patients with SCC. Upfront treatment was surgery in 84% of patients with SCC and 97% of patients with IPSCC (p = 0.18); 68 and 55% received radiation, respectively, and 25 and 21% received chemotherapy, respectively. Overall survival averaged 5.5 and 3.4 years for patients with SCC and patients with IPSCC, respectively (p = 0.12); disease-free survival was 4.8 and 2.9 years, respectively (p = 0.18). Nodal metastasis was more likely in patients with SCC (18 versus 0%; p = 0.02). When divided into high- and low-stage disease: more common nodal metastases were demonstrated in high-stage SCC than in low-stage disease (p = 0.03). Overall survival was decreased between high- and low-grade disease but not when subdivided between SCC and IPSCC. Conclusion Although SCC with and without IP association are considered different diseases, their demographics and outcomes seem similar. Nodal metastasis was noted to be higher in the SCC cohort, which may indicate different tumor biology. Further study is warranted.

Survival results of phase I dose escalation of stereotactic body radiation therapy and concurrent cisplatin for re-irradiation of unresectable, recurrent head and neck squamous cell carcinoma.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e18020-e18020
Author(s):  
Michelle Echevarria ◽  
Christine H. Chung ◽  
Kedar Kirtane ◽  
Jameel Muzaffar ◽  
Julie Ann Kish ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Overall Survival ◽  
Squamous Cell Carcinoma ◽  
Radiation Therapy ◽  
Phase I ◽  
Cell Carcinoma ◽  
Head And Neck ◽  
Squamous Cell ◽  
Stereotactic Body Radiation Therapy ◽  
Recurrent Head

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.

Salvage of Recurrence after Surgery and Adjuvant Therapy: A Multi-institutional Study

2019 ◽  
Vol 161 (1) ◽  
pp. 74-81 ◽  
Author(s):  
Joseph Zenga ◽  
Evan Graboyes ◽  
Tyler Janz ◽  
Virgina Drake ◽  
Eleni Rettig ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Adjuvant Therapy ◽  
Disease Control ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Locoregional Recurrence ◽  
Salvage Surgery ◽  
Tertiary Care ◽  
Case Series ◽  
Positive Margins

ObjectivesTo determine the oncologic outcomes of patients undergoing salvage surgery for recurrent oral cavity squamous cell carcinoma (OCSCC) and oropharyngeal squamous cell carcinoma (OPSCC) after initial treatment with surgery and adjuvant therapy.Study DesignRetrospective case series with chart review.SettingFive academic tertiary care centers.Subjects and MethodsPatients included those with OCSCC and OPSCC who were initially treated with surgery and adjuvant therapy between 2000 and 2015 and underwent salvage surgery for local and/or regional recurrence.ResultsA total of 102 patients were included (76% OCSCC, 24% OPSCC). Five-year overall survival was 31% (95% CI, 21%-41%) and was significantly improved among patients with human papillomavirus–associated oropharyngeal tumors (hazard ratio [HR], 0.34; 95% CI, 0.11-0.98) and significantly worse for those with postoperative positive margins (HR, 2.65; 95% CI, 1.43-4.93). Adjuvant (chemo)reirradiation was not associated with disease control or survival regardless of margin status. Combined locoregional recurrence was significantly correlated with a positive margin resection (HR, 5.75; 95% CI, 1.94-17.01). Twenty-five patients (25%) underwent a second salvage surgical procedure, of whom 8 achieved long-term disease control.ConclusionPatients presenting with resectable recurrence after initial therapy with surgery and adjuvant therapy have a reasonable salvage rate when a negative margin resection can be attained. Patients with postoperative positive margins have poor survival outcomes that are not significantly improved with adjuvant (chemo)reirradiation. Those with combined locoregional recurrence are at particularly high risk for postoperative positive margins. The functional consequences of salvage surgery and its effect on quality of life are critical in decision making and require further investigation.

Lack of Expression of Galectin-3 Is Associated With a Poor Outcome in Node-Negative Patients With Laryngeal Squamous-Cell Carcinoma

2002 ◽  
Vol 20 (18) ◽  
pp. 3850-3856 ◽  
Author(s):  
Mauro Piantelli ◽  
Stefano Iacobelli ◽  
Giovanni Almadori ◽  
Manuela Iezzi ◽  
Nicola Tinari ◽  
...  
Keyword(s):  
Overall Survival ◽  
Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Laryngeal Squamous Cell Carcinoma ◽  
Univariate Analysis ◽  
Prognostic Significance ◽  
Node Negative ◽  
Increased Risk ◽  
Galectin 3

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.

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