New developments in the management of head and neck cancer &amp;ndash; impact of pembrolizumab

Saleh, Khalil; Eid, Roland; Haddad, Fady G.; Khalifé-Saleh, Nadine; Kourié, Hampig Raphaël

doi:10.2147/tcrm.s125059

Cited by 60 publications

(51 citation statements)

References 56 publications

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“…Responses to immune checkpoint blockade therapy have been described in patients with colorectal cancer characterized by microsatellite instability (MSI), which is accompanied in most cases with high ML, resulting from defects in mismatch-repair pathways [22]. High ML, MSI (surrogate marker of high ML), and neoantigen production have been demonstrated to be promising markers of sensitivity to immune checkpoint blockade for several tumors [23][24][25]. However, these criteria also exhibited inconsistent patterns in patients with ovarian and urothelial cancer as well as those with glioblastoma; therefore, their potential use as prognostic factors requires further studies [26][27][28].…”

Section: Introductionmentioning

confidence: 99%

Mutational load in carotid body tumor

et al. 2019

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Background: Carotid body tumor (CBT) is a rare neoplasm arising from paraganglion located near the bifurcation of the carotid artery. There is great intra-tumor heterogeneity, and CBT development could be associated with both germline and somatic allelic variants. Studies on the molecular genetics of CBT are limited, and the molecular mechanisms of its pathogenesis are not fully understood. This work is focused on the estimation of mutational load (ML) in CBT. Methods: Using the NextSeq 500 platform, we performed exome sequencing of tumors with matched lymph node tissues and peripheral blood obtained from six patients with CBT. To obtain reliable results in tumors with low ML, we developed and successfully applied a complex approach for the analysis of sequencing data. ML was evaluated as the number of somatic variants per megabase (Mb) of the target regions covered by the Illumina TruSeq Exome Library Prep Kit. Results: The ML in CBT varied in the range of 0.09-0.28/Mb. Additionally, we identified several pathogenic/likely pathogenic somatic and germline allelic variants across six patients studied (including TP53 variants). Conclusions: Using the developed approach, we estimated the ML in CBT, which is much lower than in common malignant tumors. Identified variants in known paraganglioma/pheochromocytoma-causative genes and novel genes could be associated with the pathogenesis of CBT. The obtained results expand our knowledge of the mutation process in CBT as well as the biology of tumor development.

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Section: Introductionmentioning

confidence: 99%

Mutational load in carotid body tumor

et al. 2019

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“…In all head and neck cancers, multidisciplinary strategy should be used, the treatment choice for head and neck cancers is based on the site or extension of the primary tumor [2]. In different combinations, surgery, radiation, and chemotherapy are used to manage HNC.…”

Section: Discussionmentioning

confidence: 99%

“…Early-stage disease (stage I and stage II) is generally handled with surgery or radiation alone. Treatment involves platinum-based chemo radiation, with or without induction chemotherapy (IC) as a sequential therapy for most patients with locally advanced disease (stage III and IVA/B [2]).…”

Section: Discussionmentioning

confidence: 99%

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Evaluation of Xerostomia in Patients with Head and Neck Squamous Cell Carcinoma Treated with Radiotherapy

Mansy¹,

Salama²,

Khairallah³

et al. 2020

JCT

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Background: The sixth most prevalent cancer in the world is head and neck squamous cell carcinoma (HNSCC). In multiple combinations, surgery, radiation and chemotherapy are used in HNC control. As radiation-induced salivary gland damage and xerostomia is one of the most usual and distressing impacts, diffusion-weighted magnetic resonance imaging (DW-MRI) is a promising technique for the assessment of alterations due to radiation therapy. The aim of the study is to evaluate the effect of Chemoradiotherapy either concurrent or sequential/RTH on salivary glands using DW-MRI performed before and after chemoradiotherapy/RTH, correlation between DW-MRI changes and delivered radiation dose to salivary glands, study the acute toxicity of chemoradiotherapy/RTH on salivary glands and assess quality of life for patients with radiation-induced xerostomia. Patients and Methods: This prospective study included 43 patients with Head and Neck squamous cell carcinoma treated with definitive radiotherapy, sequential therapy or concurrent chemoradiotherapy at Clinical Oncology and Nuclear Medicine Department, MRI diffusion scans were done at Diagnostic Radiology Department Tanta University Hospitals throughout the period from May 2016 to May 2019. DW-MRI performed before and after RTH. For patients receiving CCRTH, DW sequence will be performed before starting RTH and 2-3 months post-RTH once at rest and then repeated continuously during salivary stimulation by ascorbic acid. In case of induction chemotherapy, DW-MRI was done before and after induction and 2-3 months post-RTH. Results: In all time periods, ADC values were lower for the PG than the SMG. ADC change of PGs was higher in hypopharyngeal carcinoma, while ADC change of SMGs How to cite this paper: Mansy, A

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“…HNSCC is among the seven most common malignancies worldwide. The development of HNSCC is related to tobacco use and alcohol consumption, as the most identified risk factors, but human papilloma virus (HPV), a sexually transmitted infection, has increasing significance as another primary cause of HNSCC [ 24 ]. HPV-positive tumors not only have a different etiology, but they also remarkably better respond to radio(chemo)therapy [ 25 ], as well as surgery [ 26 ], compared to HPV-negative tumors.…”

Section: Introductionmentioning

confidence: 99%

Nerve Growth Factor (NGF)—Receptor Survival Axis in Head and Neck Squamous Cell Carcinoma

Dudás

Dietl

Romani

et al. 2018

IJMS

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Neurotrophins and their receptors might regulate cell survival in head and neck squamous cell carcinoma (HNSCC). mRNA expression of nerve growth factor (NGF) and protein synthesis of high (NTRK1) and low affinity neurotrophin (p75 neurotrophin receptor; NTR) receptors were investigated in normal oral mucosa and in HNSCC. HNSCC cell lines were treated with mitomycin C (MMC) and cell survival was investigated. Normal and malignant epithelial cells expressed NGF mRNA. NTRK1 was upregulated in 80% of HNSCC tissue, and 50% of HNSCC samples were p75NTR positive. Interestingly, in HNSCC tissue: NTRK1 and p75NTR immunohistochemical reactions were mutually exclusive. Detroit 562 cell line contained only p75NTR, UPCI-SCC090 cells synthesized NTRK1 but not p75NTR and SCC-25 culture had p75NTR and NTRK1 in different cells. NGF (100 ng/mL) significantly improved (1.4-fold) the survival of cultured UPCI-SCC090 cells after MMC-induced cell cycle arrest, while Detroit 562 cells with high levels of p75NTR did not even get arrested by single short MMC treatment. p75NTR in HNSCC might be related with NGF-independent therapy resistance, while NTRK1 might transduce a survival signal of NGF and contribute in this way to improved tumor cell survival after cell cycle arrest.

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New developments in the management of head and neck cancer – impact of pembrolizumab

Cited by 60 publications

References 56 publications

Mutational load in carotid body tumor

Mutational load in carotid body tumor

Evaluation of Xerostomia in Patients with Head and Neck Squamous Cell Carcinoma Treated with Radiotherapy

Nerve Growth Factor (NGF)—Receptor Survival Axis in Head and Neck Squamous Cell Carcinoma

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