Head and Neck Squamous Cell Carcinoma (HNSCC) Protein Profiles Associated with Tumor Response to Treatment

Radiotherapy and cisplatin lead to cell killing in head and neck squamous cell carcinoma patients, but adverse events and response to treatment are not the same in patients with similar clinicopathological aspects. The aim of this prospective study was to evaluate the roles of TP53 c.215G > C, FAS c.-671A > G, FAS c.-1378G > A, FASL c.-844 C > T, CASP3 c.-1191A > G, and CASP3 c.-182-247G > T single nucleotide variants in toxicity, response rate, and survival of cisplatin chemoradiation-treated head and neck squamous cell carcinoma patients. Genomic DNA was analyzed by polymerase chain reaction for genotyping. Differences between groups of patients were analyzed by chi-square test or Fisher’s exact test, multiple logistic regression analysis, and Cox hazards model. One hundred nine patients with head and neck squamous cell carcinoma were enrolled in study. All patients were smokers and/or alcoholics. Patients with FAS c.-671GG genotype, FAS c.-671AG or GG genotype, and FASL c.-844CC genotype had 5.52 (95% confidence interval (CI): 1.42–21.43), 4.03 (95% CI: 1.51–10.79), and 5.77 (95% CI: 1.23–27.04) more chances of presenting chemoradiation-related anemia of grades 2–4, lymphopenia of grade 3 or 4, and ototoxicity of all grades, respectively, than those with the remaining genotypes. FAS c.-671GG genotype was also seen as an independent predictor of shorter event-free survival (hazard ratio (HR): 2.05; P = 0.007) and overall survival (HR: 1.83; P = 0.02) in our head and neck squamous cell carcinoma patients. These findings present, for the first time, preliminary evidence that inherited abnormalities in apoptosis pathway, related to FAS c.-671A > G and FASL c.-844 C > T single nucleotide variants, can alter toxicity and survival of tobacco- and alcohol-related head and neck squamous cell carcinoma patients homogeneously treated with cisplatin chemoradiation.

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mTOR inhibitor use in head and neck squamous cell carcinoma: A meta‐analysis on survival, tumor response, and toxicity

Laryngoscope Investigative Otolaryngology ◽

10.1002/lio2.370 ◽

2020 ◽

Vol 5 (2) ◽

pp. 243-255

Author(s):

Jaimin Patel ◽

Shaun A. Nguyen ◽

Besim Ogretmen ◽

Jorge S. Gutkind ◽

Cherie‐Ann Nathan ◽

...

Keyword(s):

Squamous Cell Carcinoma ◽

Cell Carcinoma ◽

Head And Neck ◽

Squamous Cell ◽

Mtor Inhibitor ◽

Tumor Response ◽

Meta Analysis ◽

Neck Squamous Cell Carcinoma

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A phase I, single-center, open-label study of RM-1929 photoimmunotherapy in Japanese patients with recurrent head and neck squamous cell carcinoma

International Journal of Clinical Oncology ◽

10.1007/s10147-021-01960-6 ◽

2021 ◽

Author(s):

Makoto Tahara ◽

Susumu Okano ◽

Tomohiro Enokida ◽

Yuri Ueda ◽

Takao Fujisawa ◽

...

Keyword(s):

Squamous Cell Carcinoma ◽

Cell Carcinoma ◽

Head And Neck ◽

Squamous Cell ◽

Tumor Response ◽

Japanese Patients ◽

Neck Squamous Cell Carcinoma ◽

Application Site ◽

Site Pain ◽

Recurrent Head

Abstract Background To determine the safety, preliminary efficacy, pharmacokinetics, and immunogenicity of a single cycle of RM-1929 photoimmunotherapy, an anti-EGFR antibody cetuximab conjugated with a light-activatable dye (IRDye®700DX), in Japanese patients with recurrent head and neck squamous cell carcinoma (rHNSCC). Methods Patients received a single fixed dose (640 mg/m2) of RM-1929 and a fixed light treatment dose (50 J/cm2 for superficial illumination; 100 J/cm fiber diffuser length for interstitial illumination). Safety, tumor response (modified RECIST v1.1 by central radiology review), pharmacokinetics, and immunogenicity were evaluated. Results Three Japanese patients were enrolled who had failed ≥ 3 prior lines of therapy including radiation, chemotherapy, cetuximab, and immunotherapy. Target lesions were: submental lesion; right superficial cervical node lesion and oropharynx lesion; and external auditory canal lesion. All patients experienced ≥ 1 treatment-emergent adverse event (TEAE), but none were considered dose-limiting. TEAEs were mild to moderate in severity except for one grade 3 application-site pain, which was transient, resolved without sequelae within 24 h, and did not affect study treatment administration. Thirteen of 17 TEAEs reported were possibly or probably related to study treatment. Three patient reports of application-site pain and localized edema were deemed probably related to study treatment. Objective response was observed in two patients (both partial responses). The third patient had disease progression. RM-1929 concentrations and pharmacokinetic parameters were similar in all patients. No patients tested positive for anti-drug antibodies. Conclusions RM-1929 photoimmunotherapy showed a manageable safety profile in rHNSCC. Tumor response in these heavily pre-treated patients was clinically meaningful and warrants further investigation. Clinical trial registration The trial was registered with the Japanese registry of clinical trials as jRCT2031200133.

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Impact of gene polymorphisms on toxicity and response rate in head and neck squamous cell carcinoma: a literature review

10.21203/rs.3.rs-1217709/v1 ◽

2022 ◽

Author(s):

hamid abbaszadeh ◽

Mahdieh Rajabi-Moghaddam

Keyword(s):

Squamous Cell Carcinoma ◽

Targeted Therapy ◽

Cell Carcinoma ◽

Head And Neck ◽

Squamous Cell ◽

Gene Polymorphisms ◽

Response To Therapy ◽

Neck Squamous Cell Carcinoma ◽

Response To Treatment ◽

The Impact

Abstract Advanced head and neck squamous cell carcinoma (HNSCC) is treated with radiotherapy, chemotherapy, targeted therapy or a combination of these treatments. Variations in toxicity and response to therapy are observed among patients despite similar clinicopathologic characteristics which are attributed to single nucleotide polymorphisms (SNPs). The aim of this review was to evaluate the impact of SNPs on toxicity and response to therapy in HNSCCs. A web-based search of all original articles about the impact of gene polymorphisms on toxicity and response to therapy in HNSCCs was done until September 2021 using international English language databases including Google Scholar, Scopus, PubMed and Web of science. Findings were categorized by type of treatment (radiotherapy, chemotherapy, targeted therapy, or combination therapy). In each category, studies related to growth control genes, cell proliferation, apoptosis, DNA repair genes, antioxidant and drug detoxification genes, genes of drug metabolizing enzymes, tissue remodeling genes and genes of antibody-dependent cellular cytotoxicity were discussed separately. Among studied SNPs with probable impact on toxicity and response to therapy are XRCC1, XRCC3, RAD51, Ku70, NBN, CAT, GSTP1, GSTT1, GSTM1, XPD, XPC, ERCC1, MMP3, ACSL6, EXO1, CXP2D6, FcγRIIIa, AurkA, and EGFR. Understanding gene polymorphisms will help us move toward personalized medicine and determine which patients will actually benefit from therapies for HNSCCs. By examining the SNPs, it is possible to make predictions about the patient's response to treatment or development of toxicity after treatment, and if necessary, make changes in the patient's treatment regimen.

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The Aurora-Kinase A Phe31-Ile polymorphism as possible predictor of response to treatment in head and neck squamous cell carcinoma

Oncotarget ◽

10.18632/oncotarget.24355 ◽

2018 ◽

Vol 9 (16) ◽

pp. 12769-12780 ◽

Cited By ~ 2

Author(s):

Alexander Baumann ◽

Anna Maria S. Buchberger ◽

Guido Piontek ◽

Dominik Schüttler ◽

Martina Rudelius ◽

...

Keyword(s):

Squamous Cell Carcinoma ◽

Cell Carcinoma ◽

Head And Neck ◽

Squamous Cell ◽

Aurora Kinase ◽

Neck Squamous Cell Carcinoma ◽

Response To Treatment ◽

Aurora Kinase A ◽

Kinase A

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Circulating Tumor Cells as a Prognostic Factor in Recurrent or Metastatic Head and Neck Squamous Cell Carcinoma: The CIRCUTEC Prospective Study

Clinical Chemistry ◽

10.1373/clinchem.2019.305904 ◽

2019 ◽

Vol 65 (10) ◽

pp. 1267-1275 ◽

Cited By ~ 9

Author(s):

Renaud Garrel ◽

Martine Mazel ◽

Françoise Perriard ◽

Marie Vinches ◽

Laure Cayrefourcq ◽

...

Keyword(s):

Squamous Cell Carcinoma ◽

Cell Carcinoma ◽

Head And Neck ◽

Tumor Cells ◽

Circulating Tumor Cells ◽

Squamous Cell ◽

Neck Squamous Cell Carcinoma ◽

Response To Treatment ◽

Rank Test ◽

Response To Chemotherapy

Abstract BACKGROUND This prospective multicenter study evaluated the prognostic value of circulating tumor cells (CTCs) in relapsing nonoperable or metastatic head and neck squamous cell carcinoma (rHNSCC) treated by chemotherapy and cetuximab. METHODS In 65 patients suitable for analyses, peripheral blood was taken at day 0 (D0) D7, and D21 of treatment for CTC detection by CellSearch®, EPISPOT, and flow cytometry (FCM). Progression-free survival (PFS) was assessed with the Kaplan–Meier method and compared with the log-rank test (P < 0.05). RESULTS At D0, CTCs were detected with EPISPOT, CellSearch, and FCM in 69% (45/65), 21% (12/58), and 11% (7/61) of patients, respectively. In the patients tested with all 3 methods, EPISPOT identified 92% (36/39), 92% (35/38), and 90% (25/28) of all positive samples at D0, D7, and D21, respectively. Median PFS time was significantly lower in (a) patients with increasing or stable CTC counts (36/54) from D0 to D7 with EPISPOTEGFR (3.9 vs 6.2 months; 95% CI, 5.0–6.9; P = 0.0103) and (b) patients with ≥1 CTC detected with EPISPOT or CellSearch® (37/51) (P = 0.0311), EPISPOT or FCM (38/54) (P = 0.0480), and CellSearch or FCM (11/51) (P = 0.0005) at D7. CONCLUSIONS CTCs can be detected before and during chemotherapy in patients with rHNSCC. D0–D7 CTC kinetics evaluated with EPISPOTEGFR are associated with the response to treatment. This study indicates that CTCs can be used as a real-time liquid biopsy to monitor the early response to chemotherapy in rHNSCC. ClinicalTrials.gov Identifier NCT02119559

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Genomic landscape of head and neck cancers.

Journal of Clinical Oncology ◽

10.1200/jco.2020.38.15_suppl.e18530 ◽

2020 ◽

Vol 38 (15_suppl) ◽

pp. e18530-e18530

Author(s):

Anand Subash ◽

Vishal Uchila Shishir Rao

Keyword(s):

Squamous Cell Carcinoma ◽

Cell Carcinoma ◽

Head And Neck ◽

Squamous Cell ◽

Mutation Frequency ◽

Neck Squamous Cell Carcinoma ◽

Response To Treatment ◽

Western World ◽

Novel Mutations ◽

Dna Damage And Repair

e18530 Background: Head and neck squamous cell carcinoma (HNSCC) encompasses a heterogeneous group of tumours. In India it accounts for about 40% of all the malignancies. HNSCC in the subcontinent behaves differently as compared to the western world. As heterogenous as they are so are their response to treatment. Deciphering the human genome has indeed been one of the biggest contribution to science. Genomic profiling would help identify the variants that separate these HNSCC patients and facilitate development of newer targeted therapeutic strategies. Methods: At Healthcare Global Cancer Centre, Bangalore we retrospectively analysed 35 cases of Head and Neck squamous cell carcinoma as a pilot. Whole exome analysis of the patient samples were done using the Illumina Hi-Seq 2500 machine with a depth of 70-100X. Results: Of the 35 patients, 27 were oral cavity squamous cell carcinoma. About 2/3rd of these patients had history of tobacco or alcohol use. At the time of analysis 20 patients were alive and disease free,3 were alive with disease,11 were dead and 2 were lost to follow up. It was observed that the maximum number of variations were mis-sense mutations. Known oncogenic proteins like TP53 and NOTCH1 showed a mutation frequency of more than 50%, while DNA damage and repair genes like XRCC1 and ERCC2 were seen to have almost 90% mutation frequency, some of which have not been previously documented in literature. Conclusions: The preliminary data has brought to light some very novel mutations, many of them until now unknown to be implicated in HNSCC. This study holds the potential to predict response to treatment and factors which contribute to this. We have classified these novel mutations into different pathways so that specific targeted therapies can be developed in future.

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