Recent results of cetuximab use in the treatment of squamous cell carcinoma of the head and neck

Cetuximab is a chimeric monoclonal antibody that targets the epidermal growth factor receptor. The role of cetuximab is paramount in several subsets of head and neck cancer. In particular, the EXTREME study has indicated cetuximab as the only drug to improve survival when associated with cisplatin and 5-fluorouracil in patients with recurrent/metastatic disease. Furthermore, cetuximab, both alone and in combination with cisplatin, is active in patients with recurrent/metastatic disease who have failed prior platinum-based chemotherapy. Cetuximab, given in association with radiation therapy, is a treatment of choice in first-line therapy of patients with locally advanced inoperable disease. In the same setting, the role of induction chemotherapy has gained considerable interest over the last few years and a number of efforts are being pursued to optimally integrate induction chemotherapy with radiation therapy plus cetuximab. The combination of cetuximab and other targeted therapies is among the most promising new perspectives for patients with head and neck cancer

Electrochemotherapy as palliative treatment in patients with advanced head and neck tumours: Outcome analysis in 93 patients treated in a single institution.

Abstract Purpose To describe outcomes of Electrochemotherapy as palliative treatment in patients with advanced head and neck (H&N) tumours. Methods Ninety-three patients (120 treatment sessions) with H&N recurrent and/or metastatic neoplasm were treated. Treatment response was assessed 4 weeks after ECT with clinical examination and two months after the first evaluation with a CT scan of the H&N for deep lesions evaluation. The grade of bleeding and pain before, at the end of treatment and one week after ECT were evaluated. Results Five percent of complete responses, 40% of partial responses were registered. Disease progression was seen in 20% of patients after the first ECT procedure, the remaining 34% of patients experienced stable disease. A good control of pain and bleeding was obtained, especially in patients with moderate symptoms before the treatment. No toxicities related to ECT were seen. Conclusions ECT is an interesting antitumoral therapy in advanced chemo and radio-refractory H&N neoplasms. ECT is able to reduce frequent symptoms, such as pain and bleeding, improving quality of life without damage to healthy tissue and with limited side effects. Moreover, ECT reduces hospitalization time and may contribute to an overall reduction in healthcare costs associated with advanced H&N cancers care

Quantitative assessment of dimensional evolution of solitary osteoma of the mandible through 14 years of radiographic follow-up analysis: A unique case report

Abstract Head & Neck Osteomas are extremely rare osteogenic benign tumors, with unclear pathogenesis and heterogeneous clinical behavior. There are no studies in literature showing the characteristics of dimensional growth of such lesions. We report a case of a peripheral solitary osteoma of the sigmoid notch of the mandibular ramus, describing its radiographic growth in fourteen years. Measurements from OPTs (2003–6x7mm, 2008–8x12mm, 2014–17 × 24mm, 2016–19 × 25mm and 2017–21 × 28mm) and 3d cone-beam computed tomography scan (2016–19 × 15 × 21mm, 2017–21,4 × 19,2 × 22,7) were obtained. The growth of the lesion measured on OPTs was in mean 1.1 × 1.5 mm per year. This is the first case report in literature quantitatively assessing the growth of a solitary osteoma of the mandible through radiographic imaging, which seems to be more than 1 mm per dimension per year

Leiomyosarcoma of the Oropharynx and Neurogenic Tumors in a Young Patient With Turner's Syndrome

Patient: A case of Turner's syndrome developing a leiomyosarcoma of the oropharynx and metachronous neurogenic tumors (mediastinal ‘ganglioneuroblastoma intermixed’, subcutaneous neurilemoma) is described

Speech outcome in tongue cancer surgery: objective evaluation by acoustic analysis software

BACKGROUND. Cancer of the oral cavity is one of the most common malignancies of which 60% affect the tongue. Carcinoma of the tongue causes significant alterations of the articulatory and swallowing functions. The gold standard of care remains primary surgical resection with or without postoperative adjuvant therapy. Whereas T1 and T2 tongue tumors can be treated with more conservative surgeries, as partial glossectomies, the larger tumors require total and aggressive glossectomies which increase survival, but, on the other hand, they might often make speech, chewing and swallowing impossible. MATERIAL AND METHODS. Our study was performed on a total of 21 patients with Squamous Cell Carcinoma of the tongue who underwent either partial resection or hemiglossectomy. Each subject (either surgical patients or controls) was asked to pronounce the vowels /a/, /e/, /i/, /u/, and all signals were evaluated separately by two operators. Acoustic (F0, jitter, shimmer, NHR) and vowel metric (the ratio F2i/F2u, tVSA, qVSA, FCR) features have been extracted. In order to define the speech intelligibility, all patients were evaluated by two doctors and one speech therapist and all patients received the Speech Handicap Index (SHI) translated into Italian language before recording. RESULTS. No statistically significant variations were observed, regardless of the gender, between controls and surgically resected patients when tumor staging was T1-T2. On the contrary, when patients had to undergo more extensive surgical resection due to the presence of a T3-T4 tumor, a dramatic increase of F2u could be observed. This change, together with a decrease of F2i, led to a highly significant reduction in the F2i/F2u parameter in surgically resected patients as compared to controls. The other parameters which were reduced in a statistically significant manner in T3-T4 surgically resected patients were tVSA and qVSA. Instead, two parameters increased in a statistically significant manner in T3-T4 surgically resected patients: FCR and SHI. Again, none of the above-mentioned parameters was altered in a statistically significant manner in early tumor stage resected patients, regar dless of the gender. CONCLUSION. For the first time, we used a series of newly developed formant parameters, introduced by various authors for the study of the articulatory undershoot of the tongue in various neurodegenerative diseases. The statistical analysis of our results highlighted in an incontrovertible way a strong correlation and significance of each of our parameters F2 / i / / F2 / u /, FCR, tVSA, qVSA, with the entity of the TNM, and therefore of the surgical extension of the resection, and in parallel with the loss of the intelligibility of the speech that proportionally reaches higher values in the advanced stages of the disease as can be deduced from the SHI trend

Valproic Acid Synergizes With Cisplatin and Cetuximab in vitro and in vivo in Head and Neck Cancer by Targeting the Mechanisms of Resistance

Recurrent/metastatic head and neck squamous cell carcinoma (R/M HNSCC) is a devastating malignancy with a poor prognosis. The combination of cisplatin (CDDP) plus cetuximab (CX) is one of the standard first-line treatments in this disease. However, this therapeutic regimen is often associated with high toxicity and resistance, suggesting that new combinatorial strategies are needed to improve its therapeutic index. In our study, we evaluated the antitumor effects of valproic acid (VPA), a well-known antiepileptic agent with histone deacetylase inhibitory activity, in combination with CDDP/CX doublet in head and neck squamous cell carcinoma (HNSCC) models. We demonstrated, in HNSCC cell lines, but not in normal human fibroblasts, that simultaneous exposure to equitoxic doses of VPA plus CDDP/CX resulted in a clear synergistic antiproliferative and pro-apoptotic effects. The synergistic antitumor effect was confirmed in four different 3D-self-assembled spheroid models, suggesting the ability of the combined approach to affect also the cancer stem cells compartment. Mechanistically, VPA enhanced DNA damage in combination treatment by reducing the mRNA expression of ERCC Excision Repair 1, a critical player in DNA repair, and by increasing CDDP intracellular concentration via upregulation at transcriptional level of CDDP influx channel copper transporter 1 and downregulation of the ATPAse ATP7B involved in CDDP-export. Valproic acid also induced a dose-dependent downregulation of epidermal growth factor receptor (EGFR) expression and of MAPK and AKT downstream signaling pathways and prevent CDDP- and/or CX-induced EGFR nuclear translocation, a well-known mechanism of resistance to chemotherapy. Indeed, VPA impaired the transcription of genes induced by non-canonical activity of nuclear EGFR, such as cyclin D1 and thymidylate synthase. Finally, we confirmed the synergistic antitumor effect also in vivo in both heterotopic and orthotopic models, demonstrating that the combined treatment completely blocked HNSCC xenograft tumors growth in nude mice. Overall, the introduction of a safe and generic drug such as VPA into the conventional treatment for R/M HNSCC represents an innovative and feasible antitumor strategy that warrants further clinical evaluation. A phase II clinical trial exploring the combination of VPA and CDDP/CX in R/M HNSCC patients is currently ongoing in our institute

Global wealth disparities drive adherence to COVID-safe pathways in head and neck cancer surgery

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Whole-genome sequence-based analysis of thyroid function

Tiina Paunio on työryhmän UK10K Consortium jäsen.Normal thyroid function is essential for health, but its genetic architecture remains poorly understood. Here, for the heritable thyroid traits thyrotropin (TSH) and free thyroxine (FT4), we analyse whole-genome sequence data from the UK10K project (N = 2,287). Using additional whole-genome sequence and deeply imputed data sets, we report meta-analysis results for common variants (MAF >= 1%) associated with TSH and FT4 (N = 16,335). For TSH, we identify a novel variant in SYN2 (MAF = 23.5%, P = 6.15 x 10(-9)) and a new independent variant in PDE8B (MAF = 10.4%, P = 5.94 x 10(-14)). For FT4, we report a low-frequency variant near B4GALT6/ SLC25A52 (MAF = 3.2%, P = 1.27 x 10(-9)) tagging a rare TTR variant (MAF = 0.4%, P = 2.14 x 10(-11)). All common variants explain >= 20% of the variance in TSH and FT4. Analysis of rare variants (MAFPeer reviewe