Statistical Methods for Biomarker Analysis for Head and Neck Carcinogenesis and Prevention

2003 ◽  
pp. 287-IV ◽  
Author(s):  
J. Jack Lee
Keyword(s):  
Head And Neck ◽  
Statistical Methods ◽  
Biomarker Analysis

Phase II Trial of Sorafenib in Patients With Recurrent or Metastatic Squamous Cell Carcinoma of the Head and Neck or Nasopharyngeal Carcinoma

2007 ◽  
Vol 25 (24) ◽  
pp. 3766-3773 ◽  
Author(s):  
Christine Elser ◽  
Lillian L. Siu ◽  
Eric Winquist ◽  
Mark Agulnik ◽  
Gregory R. Pond ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Nasopharyngeal Carcinoma ◽  
Cell Carcinoma ◽  
Head And Neck ◽  
Phase Ii ◽  
Squamous Cell ◽  
Group Performance ◽  
Phase Ii Trial ◽  
Biomarker Analysis ◽  
Metastatic Squamous Cell Carcinoma

PurposeTo determine the efficacy and safety of single-agent sorafenib in patients with recurrent and/or metastatic squamous cell carcinoma of the head and neck (SCCHN) and nasopharyngeal carcinoma (NPC).Patients and MethodsIn this single-arm phase II trial, oral continuous sorafenib was administered in 28-day cycles. Patients had ≤ one line of chemotherapy for recurrent and/or metastatic disease, Eastern Cooperative Oncology Group performance status of ≤ 2, and adequate organ function. At the end of stage 1, efficacy criteria for further accrual were not met, but the study was amended to enroll an additional five patients for paired tumor biopsies.ResultsTwenty-seven and 26 patients were eligible for toxicity and efficacy evaluations, respectively. One patient (3.7%; 95% CI, 0.1% to 19.0%) achieved a partial response. Disease stabilization was maintained in 10 patients (37.0%; 95% CI, 22.4% to 61.2%). The median time to progression was 1.8 months (95% CI, 1.6 to 3.4 months), and median overall survival time was 4.2 months (95% CI, 3.6 to 8.7 months). Sorafenib was well tolerated with few grade 3 and no grade 4 toxicities. Biomarker analysis of paired tumor samples before and after treatment with sorafenib revealed a decrease of pERK in all five patients, with a decrease in Ki67 in four patients, consistent with a disruption of ERK signaling. The antiapoptotic protein Mcl-1 was downregulated in four patients, and there was also evidence of antiangiogenic activity.ConclusionSorafenib was well tolerated and had modest anticancer activity comparable to monotherapy with other targeted agents in this group of patients. Further development in combination with radiation or other agents may be warranted.

scholarly journals New technology on the horizon: Fast analytical screening technique FNA (FAST‐FNA) enables rapid, multiplex biomarker analysis in head and neck cancers

2020 ◽  
Vol 128 (11) ◽  
pp. 782-791
Author(s):  
Sara I. Pai ◽  
William C. Faquin ◽  
Peter M. Sadow ◽  
Mikael J. Pittet ◽  
Ralph Weissleder
Keyword(s):  
Head And Neck ◽  
New Technology ◽  
Head And Neck Cancers ◽  
Screening Technique ◽  
Biomarker Analysis

scholarly journals Genomic Landscape of Angiosarcoma: A Targeted and Immunotherapy Biomarker Analysis

Cancers ◽  
2021 ◽  
Vol 13 (19) ◽  
pp. 4816
Author(s):  
Andrea P. Espejo-Freire ◽  
Andrew Elliott ◽  
Andrew Rosenberg ◽  
Philippos Apolinario Costa ◽  
Priscila Barreto-Coelho ◽  
...  
Keyword(s):  
Head And Neck ◽  
Genetic Alterations ◽  
Design And Optimization ◽  
Whole Exome ◽  
Genomic Landscape ◽  
Mutation Burden ◽  
Biomarker Analysis ◽  
Next Generation Sequencing Ngs ◽  
Response Biomarkers ◽  
Ngs Data

We performed a retrospective analysis of angiosarcoma (AS) genomic biomarkers and their associations with the site of origin in a cohort of 143 cases. Primary sites were head and neck (31%), breast (22%), extremity (11%), viscera (20%), skin at other locations (8%), and unknown (9%). All cases had Next Generation Sequencing (NGS) data with a 592 gene panel, and 53 cases had Whole Exome Sequencing (WES) data, which we used to study the microenvironment phenotype. The immunotherapy (IO) response biomarkers Tumor Mutation Burden (TMB), Microsatellite Instability (MSI), and PD-L1 status were the most frequently encountered alteration, present in 36.4% of the cohort and 65% of head and neck AS (H/N-AS) (p < 0.0001). In H/N-AS, TMB-High was seen in 63.4% of cases (p < 0.0001) and PDL-1 positivity in 33% of cases. The most common genetic alterations were TP53 (29%), MYC amplification (23%), ARID1A (17%), POT1 (16%), and ATRX (13%). H/N-AS cases had predominantly mutations in TP53 (50.0%, p = 0.0004), POT1 (40.5%, p < 0.0001), and ARID1A (33.3%, p = 0.5875). In breast AS, leading alterations were MYC amplification (63.3%, p < 0.0001), HRAS (16.1%, p = 0.0377), and PIK3CA (16.1%, p = 0.2352). At other sites, conclusions are difficult to generate due to the small number of cases. A microenvironment with a high immune signature, previously associated with IO response, was evenly distributed in 13% of the cases at different primary sites. Our findings can facilitate the design and optimization of therapeutic strategies for AS.

Statistical Methods for Detecting Genetic Interactions: A Head and Neck Squamous-Cell Cancer Study

2008 ◽  
Vol 71 (11-12) ◽  
pp. 803-815 ◽  
Author(s):  
Katja Ickstadt ◽  
Martin Schäfer ◽  
Arno Fritsch ◽  
Holger Schwender ◽  
Josef Abel ◽  
...  
Keyword(s):  
Head And Neck ◽  
Statistical Methods ◽  
Squamous Cell ◽  
Squamous Cell Cancer ◽  
Cell Cancer ◽  
Genetic Interactions ◽  
Cancer Study ◽  
Neck Squamous Cell Cancer

scholarly journals Molecular Alterations and Buparlisib Efficacy in Patients with Squamous Cell Carcinoma of the Head and Neck: Biomarker Analysis from BERIL-1

2018 ◽  
Vol 24 (11) ◽  
pp. 2505-2516 ◽  
Author(s):  
Denis Soulières ◽  
Lisa Licitra ◽  
Ricard Mesía ◽  
Éva Remenár ◽  
Shau-Hsuan Li ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Head And Neck ◽  
Squamous Cell ◽  
Molecular Alterations ◽  
Biomarker Analysis

Correlative biomarker analysis of sequential tumor biopsies in a ph I mode of action (MoA) study in neoadjuvant head and neck squamous cell carcinoma (HNSCC) patients (pts) treated with RG7160 (GA201), a novel dual-acting, monoclonal antibody (mAb) designed to enhance antibody-dependent cellular cytotoxicity (ADCC), with cetuximab (C) as reference.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 3035-3035
Author(s):  
Christoph Mancao ◽  
Lilla Di Scala ◽  
Paul Delmar ◽  
Stéphane Temam ◽  
Jean-Charles Soria ◽  
...  
Keyword(s):  
Statistical Methods ◽  
Immune Cell ◽  
Growth Factor Receptor ◽  
Immune Markers ◽  
Open Label ◽  
Immune Effector ◽  
Bivariate Correlation ◽  
Cell Counts ◽  
Biomarker Analysis ◽  
Tumor Biopsies

3035 Background: GA201 is a novel humanized anti-epidermal growth factor receptor (EGFR) mAb with a dual MoA: glycoengineered to enhance ADCC on top of inhibition of EGFR signaling. In an open-label, multi-center trial of pts with HNSCC, an exploratory biomarker analysis of sequential tumor biopsies was performed to investigate the single/duplex marker correlation structure. Methods: Pts received 2 doses of 700 or 1,400 mg GA201 or C (day 1, 8). Tumor biopsies were taken at baseline (BL) and pre-surgery (day 15). Immunohistochemistry immune-cell counts (single/duplex markers), EGFR-pathway markers and intra-tumoral cytokines (LUMINEX) were assessed. Advanced exploratory statistical methods were used to analyse inter-relationship between BL and on treatment markers, and with response (as determined by FDG-PET). Results: All immune markers (single and duplex) presented highly heterogeneous median values at BL, but cluster analysis emphasized their strong inter-correlation. These markers were unrelated to the BL tumor EGFR and pERK expression. Strongest bivariate correlation was seen between (CD16, CD68), (CD3, 4, 8) and (CD4, NKp46). GA201 treatment induced positively correlated dynamic changes (chg) between (CD8, CD68), while C did so for (CD4, CD16) and (CD16, CD68). Strong and negative correlation between (CD56chg, PETchg) was seen only in pts treated with 1,400 mg GA201. Intra-tumoral cytokines like CXCL12 showed good correlation with BL CD3, 16 and 68 infiltration. Principle component analysis also confirmed a good association between most BL immune markers and was able to differentiate strongest PET responders in the 700 mg GA201 cohort. Conclusions: Multivariate statistical methods were used to demonstrate strong interdependencies between immune-effector markers and to highlight their promising associations with response to GA201 treatment, likely due to ADCC processes in the tumors. Clinical trial information: NCT01046266.

Afatinib and pembrolizumab for recurrent or metastatic head and neck squamous cell carcinoma (ALPHA Study): A phase II study with biomarker analysis.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 6024-6024
Author(s):  
Hsiang-fong Kao ◽  
Bin-Chi Liao ◽  
Yen-Lin Huang ◽  
Huai-Cheng Huang ◽  
Chun-Nan Chen ◽  
...  
Keyword(s):  
Gene Expression ◽  
Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Head And Neck ◽  
Phase Ii ◽  
Squamous Cell ◽  
Response Rate ◽  
Phase Ii Study ◽  
Egfr Amplification ◽  
Biomarker Analysis

6024 Background: Epidermal growth factor receptor (EGFR) pathway inhibition may synergize with anti-PD1 activity by inhibiting macrophage function, increasing antigen presentation, and augmenting T cell responses. Afatinib, an irreversible EGFR tyrosine kinase inhibitor (TKI), has been shown to enhance anti-PD1 activity in in vitro and animal studies. We thus hypothesized that adding afatinib to pembrolizumab may improve the treatment outcomes for patients with recurrent or metastatic head and neck squamous cell carcinoma (HNSCC). Methods: The ALPHA study (NCT03695510) is a single-arm, phase II study with a Simon 2-stage design. Patients with platinum-refractory, recurrent, or metastatic HNSCC are eligible for the study. Afatinib (40mg, oral, daily) and pembrolizumab (200mg, every 3 weeks) are administered to eligible patients. The primary endpoint is the objective response rate (ORR). PD-L1 IHC testing (22C3), comprehensive genomic profiling (CGP, Roche Foundation Medicine One CDx), and targeted multiplexed gene expression profiling (Nanostring nCounter PanCancer Immune Profiling Panel) were applied for biomarker analysis. Results: From JAN 2019 to MAR 2020, 29 patients were enrolled in the study. Age: mean = 53.4 years old; M/F = 27/2. Tumor type: oral cavity: 19; oropharynx: 6, hypopharynx: 2, larynx: 2. PD-L1 TPS > = 50: 7/29 (24.1%), CPS > = 20: 8/29 (27.6%), TMB > 10: 0/25 (0%). The common treatment-related adverse events (AEs; all grades, grade > = 3) were skin rash (22/29, 4/29), diarrhea (17/29, 3/29), paronychia (13/29, 0/29), mucositis (9/29, 1/29), and weight loss (2/29, 0/29). One patient experienced grade 2 pneumonitis. Twelve patients had partial responses to the treatment (12/29, ORR: 41.4%). The data cut-off date was 11FEB2021. The median progression free survival (PFS) was 4.1 (95% confidence interval [CI], 1.9-6.3) months. The median overall survival (OS) was 8.4 (95% CI, 4.1-10.8) months. Patients with high PD-L1 expression had a higher response rate (TPS > = 50: ORR = 0.71, CPS > = 20: ORR = 0.63). EGFR amplification might also predict a higher response rate (ORR: 3/3, 100%). MTAP loss or mutation may predict a poor response to the treatment (ORR: 0/5, 0%), shorter PFS (HR: 4.21, [95% CI: 1.34-13.24], p = 0.014), and shorter OS (HR: 4.20 [95% CI: 1.32-13.41], p = 0.015). Nine patients underwent paired pre-treatment and post-treatment biopsies for gene expression analysis. The mRNA of HLA-A, HLA-B, CXCL13, CXCL9, and CD8A were elevated in the post-treatment biopsies. Three patients underwent post-progression biopsies for CGP study. One patient had a new MTAP mutation. Conclusions: Afatinib can modify tumor microenvironment and increase the clinical response rate in pembrolizumab-based therapy in HNSCC patients. PD-L1, EGFR amplification, and MTAP loss/mutation could be biomarkers for cancer immunotherapy. Clinical trial information: NCT03695510.

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