2006 Local tumour control after simultaneous fractionated irradiation and EGFR-blockade by monoclonal antibodies (Cetuximab) versus tyrosine kinase inhibitors (Erlotinib) in different head and neck squamous cell carcinoma (HNSCC) models

2009 ◽  
Vol 7 (2) ◽  
pp. 153 ◽  
Author(s):  
M. Krause ◽  
K. Gurtner ◽  
Y. Deuse ◽  
W. Eicheler ◽  
M. Baumann
Keyword(s):  
Squamous Cell Carcinoma ◽  
Monoclonal Antibodies ◽  
Tyrosine Kinase ◽  
Cell Carcinoma ◽  
Head And Neck ◽  
Kinase Inhibitors ◽  
Fractionated Irradiation ◽  
Tumour Control ◽  
Local Tumour Control ◽  
Local Tumour

Adjuvant Radiotherapy and Chemoradiation in Elderly Patients with Squamous Cell Carcinoma of the Head and Neck

2020 ◽  
Author(s):  
Christoph Süß ◽  
Anna Ratzisberger ◽  
Matthias Hipp ◽  
Tobias Ettl ◽  
Julian Kuenzel ◽  
...  
Keyword(s):  
Overall Survival ◽  
Squamous Cell Carcinoma ◽  
Elderly Patients ◽  
Cell Carcinoma ◽  
Head And Neck ◽  
Squamous Cell ◽  
Adjuvant Radiotherapy ◽  
Tumour Control ◽  
Local Tumour Control ◽  
Local Tumour

Abstract Background:Radiotherapy and chemoradiation are well-established therapies for patients with squamous cell carcinoma of the head and neck (SCCHN). In aging societies, also the incidence of SCCHN in elderly patients is rising. Because of the underrepresentation of elderly patients in scientific trials, we evaluated the feasibility of adjuvant radiotherapy and chemoradiation in patients with SCCHN aged >70 years. Methods:All patients had been >70 years at the time of diagnosis and received adjuvant radiotherapy or, if feasible, chemoradiation at the University Medical Centre Regensburg between 2004 and 2018.71 patients -most with SCCHN UICC stage IVa- with a median age of 75 years were included; 9 patients received concomitant chemoradiation. Median follow-up was 27 months (IQR 18 – 62 months).Results:Radiotherapy and chemoradiation was well tolerated. 62 patients (87.3%) underwent treatment without interruption, and 65 patients (91.5%) completed radiotherapy with 95% of the initially prescribed dose. Median dose for all patients was 64 Gy (IQR: 60 – 66 Gy). 6/9 patients received at least 75 % of the planned chemotherapy dose. 37 patients (52.1%) developed acute toxicity CTC grade III or IV.Overall survival was 87 % after 12 months, 67 % after 24 months and 41 % after 60 months. Median overall survival was 51 months (IQR: 19 - 99 months). Local tumour control was 99 % after 12 months, 88 % after 24 months and 76 % after 5 years.Conclusion:Feasibility of adjuvant radiotherapy and chemoradiation in our collective of elderly patients with SCCHN was good. Particularly local tumour control was satisfactory. Overall survival does not seem to differ between elderly and younger patients or patients unselected for age. De-intensification of treatment because of age does not seem justified.

scholarly journals Aberrant HER3 ligand heregulin-expressing head and neck squamous cell carcinoma is resistant to anti-EGFR antibody cetuximab, but not second-generation EGFR-TKI

Oncogenesis ◽  
2019 ◽  
Vol 8 (10) ◽  
Author(s):  
Kimio Yonesaka ◽  
Kaoru Tanaka ◽  
Mutsukazu Kitano ◽  
Hisato Kawakami ◽  
Hidetoshi Hayashi ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Tyrosine Kinase ◽  
Cell Carcinoma ◽  
Head And Neck ◽  
Tyrosine Kinase Inhibitors ◽  
Transcriptome Analysis ◽  
Kinase Inhibitors ◽  
Akt Phosphorylation ◽  
Fadu Cells ◽  
Egfr Antibody

Abstract The anti-epidermal growth factor receptor (EGFR) antibody cetuximab is standard therapy for head and neck squamous cell carcinoma (HNSCC). However, most HNSCC tumors are resistant to it and require alternative treatments. Here, we explored the mechanism of cetuximab resistance and evaluated its clinical relevance in HNSCC. An unbiased comprehensive transcriptome analysis was performed on cetuximab-resistant HNSCC FaDuCR cells. The causative resistance genome was knocked down with siRNA, cell signaling was immunologically analyzed, and drug efficacy was evaluated in vitro and in vivo. The mRNA in situ hybridization (ISH) of the causative genome was performed using 28 excised HNSCC tumors and its relationship with cetuximab efficacy was analyzed. FaDuCR cells were resistant to cetuximab, whereas parental FaDu cells were susceptible to it. FaDuCR cells expressed consistently higher levels of phosphorylated Akt than FaDu cells despite cetuximab exposure. A comprehensive transcriptome analysis revealed that the HER3-ligand heregulin was upregulated in FaDuCR cells compared to FaDu cells. Heregulin knockdown in FaDuCR cells repressed HER3 and Akt phosphorylation and recovered cetuximab anticancer efficacy. In contrast, pan-HER family tyrosine kinase inhibitors such as afatinib decreased HER3 and Akt phosphorylation in FaDuCR cells and inhibited FaDuCR tumor growth. Two of the 28 HNSCC tumor samples presented aberrant heregulin expression comparable to that of FaDuCR cells and were resistant to cetuximab therapy. In HNSCC, heregulin-mediated HER3-Akt activation causes resistance to cetuximab but not to second-generation EGFR-tyrosine kinase inhibitors. Subpopulations with aberrant heregulin-expressing HNSCC might be resistant to cetuximab.

Genomic Alterations in Head and Neck Squamous Cell Carcinoma: Level of Evidence According to ESMO Scale for Clinical Actionability of Molecular Targets (ESCAT)

2021 ◽  
pp. 215-226
Author(s):  
Grégoire Marret ◽  
Ivan Bièche ◽  
Célia Dupain ◽  
Edith Borcoman ◽  
Pauline du Rusquec ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Tyrosine Kinase ◽  
Cell Carcinoma ◽  
Head And Neck ◽  
Squamous Cell ◽  
Molecular Targets ◽  
Level Of Evidence ◽  
Egfr Amplification ◽  
Molecular Alterations ◽  
Activating Mutations

Development of high-throughput technologies helped to decipher tumor genomic landscapes revealing actionable molecular alterations. We aimed to rank the level of evidence of recurrent actionable molecular alterations in head and neck squamous cell carcinoma (HNSCC) on the basis of the European Society for Medical Oncology (ESMO) Scale for Clinical Actionability of Molecular Targets (ESCAT) to help the clinicians prioritize treatment. We identified actionable alterations in 33 genes. HRAS-activating mutations were ranked in tier IB because of the efficacy of tipifarnib (farnesyltransferase inhibitor) in HRAS-mutated patients with HNSCC (nonrandomized clinical trial). Microsatellite instability (MSI), high tumor mutational burden (TMB), and NTRK fusions were ranked in tier IC because of PD-1 and TRK tyrosine kinase inhibitors tissue-agnostic approvals. CDKN2A-inactivating alterations and EGFR amplification were ranked in tier IIA because of the efficacy of palbociclib (CDK4/6 inhibitor) and afatinib (tyrosine kinase inhibitor) in these respective molecular subgroups in retrospective analyses of clinical trials. Molecular alterations in several genes, including PIK3CA gene, were ranked in tier IIIA because of clinical benefit in other tumor types, whereas molecular alterations in IGF1R and TP53 genes were ranked in tier IVA and tier V, respectively. The most compelling actionable molecular alterations in HNSCC according to ESCAT include HRAS-activating mutations, MSI, high TMB, NTRK fusions, CDKN2A-inactivating alterations, and EGFR amplification.

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