scholarly journals Consistent administration of cetuximab is associated with favorable outcomes in recurrent/metastatic head and neck squamous cell carcinoma in an endemic carcinogen exposure area: a retrospective observational study

PeerJ ◽  
2020 ◽  
Vol 8 ◽  
pp. e9862
Author(s):  
Hui-Ching Wang ◽  
Pei-Lin Liu ◽  
Pei-Chuan Lo ◽  
Yi-Tzu Chang ◽  
Leong-Perng Chan ◽  
...  

Background This study aimed to analyze the clinical outcomes associated with patients with recurrent/metastatic head and neck squamous cell carcinoma (RM HNSCC) who received cetuximab-based chemotherapy in a real-world clinical setting. Methods Clinical data were extracted from RM HNSCC patients diagnosed between 2016 and 2019. Kaplan–Meier survival estimates and Cox proportional hazards model were used for survival analyses. Results Of 106 RM HNSCC patients (mean age = 55.1 years), 38.7% exhibited recurrent disease and 61.3% had metastatic disease. The majority of patients showed a habit of addictive substance use, including alcohol (67.0%), betel nuts (71.7%), or tobacco (74.5%). The primary tumor sites included the oral cavity (64.1%), hypopharynx (19.8%), and oropharynx (16.0%). The median number of cetuximab cycles for the 106 patients was 11 (2–24). The disease control rate (DCR) was 48.1%, and the overall response rate (ORR) was 28.3%. The median progression-free survival (PFS) and overall survival (OS) were 5.0 and 9.23 months, respectively. Patients treated with more than 11 cycles of cetuximab exhibited a longer median PFS and median OS than did patients treated with less than 11 cycles (median PFS: 7.0 vs. 3.0 months, p < 0.001; OS: 12.43 vs. 4.46 months, p = 0.001). Patients without previous concurrent chemoradiotherapy (CRT) had a better median PFS than did those with previous CRT (6.0 vs. 4.0 months, p = 0.046). Multivariable analysis revealed that perineural invasion and fewer cycles of cetuximab (<11 cycles) were independent risk factors associated with disease progression. In addition, the reduction in treatment cycles of cetuximab and advanced lymph node metastasis were independent prognostic factors predicting poorer overall survival. Conclusion Our study provides important real-world data regarding cetuximab-containing treatment in RM HNSCC. Consistent administration of cetuximab could be associated with more favorable outcomes in RM HNSCC in endemic carcinogen exposure areas.

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.


2020 ◽  
Vol 4 (3) ◽  
pp. 105
Author(s):  
Manikandan Dhanushkodi ◽  
Vijay Gnanaguru ◽  
Venkatraman Radhakrishnan ◽  
JayachandranPerumal Kalaiarasi ◽  
ArunKumar Rajan ◽  
...  

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e18512-e18512
Author(s):  
Bruna Bighetti ◽  
José Tristão Neto ◽  
Renata do Socorro Monteiro Pereira ◽  
LAÍS CRISTHINE SOUZA ◽  
Ilka Lopes Santoro ◽  
...  

e18512 Background: Cisplatin-based chemoradiotherapy (CRT) is a well-established regimen used for adjuvant and/or head-and-neck squamous cell carcinoma (HNSCC) radical treatment. The most classic protocol for chemoradiotherapy remains the administration of Cisplatin 100mg/m² EV D1 q3-week period, 3 cycles. The objective of this study is to assess the efficacy and tolerability of the weekly 40mg/m² cisplatin regimen. Methods: we conducted a retrospective study from 2007-2020 with 102 patients treated at a national reference institution. All of them with HNSCC received concurrent CRT with weekly cisplatin 40mg/m² EV D1. We analyzed the overall survival (OS), local recurrence and tolerability in this scheme. Results: The median cisplatin cumulative dose received by our patients was 240mg/m². Hence, we divided them in two groups for the analysis: Group A (41 patients) received less than 240mg/m² cisplatin total dose and Group B (61 patients) received more or equal 240mg/m² cisplatin total dose. Both groups were equally balanced between sex, clinic stage, histologic grade and clinic status. We found that the Group A experienced 5 deaths (12.2%) while the Group B experienced 6 deaths (9.8%). The mean time to recurrence disease in the Group A was 45.68 months and in Group B 60.22 months (p = 0.958). The estimated overall survival in the Group A was 150 months and in the Group B was 116.4 months (p = 0.443). Conclusions: The weekly cisplatin dose regimen showed to be feasible, more tolerable, and less toxic and with no difference in terms of OS then the classic 3-week cisplatin protocol in the CRT setting. Our group suggests that the 240mg/m² cumulative cisplatin weekly schedule should be a better option for CRT treatments then the classic cisplatin regimen. A phase III clinical trial is warranted to further understanding of this framework. Key-words: head and neck cancer, cisplatin, radiotherapy


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