EGFR R521K Polymorphism Is Not a Major Determinant of Clinical Cetuximab Resistance in Head and Neck Cancer.

Background: Head and neck squamous cell carcinomas (HNSCCs) are among the most abundant malignancies worldwide. Patients with recurrent/metastatic disease undergo combination chemotherapy containing cetuximab, the monoclonal antibody used against the epidermal growth factor receptor (EGFR). Cetuximab augments the effect of chemotherapy; however, a significant number of patients show therapy resistance.

Prognostic factor analysis and long-term results of the TAX 323 (EORTC 24971) study in unresectable head and neck cancer patients.

Background: In the TAX 323 (EORTC 24971) phase III trial enrolling patients with unresectable locoregionally advanced squamous cell carcinoma of the head and neck (LA-SCCHN), the addition of docetaxel (T) to cisplatin and 5-fluorouracil (PF)-based induction chemotherapy prior to definite radiotherapy significantly improved progression-free survival (PFS) and overall survival (OS).

Methods: The data were updated for PFS, OS and treatment-related long-term side-effects. Baseline clinical and laboratory data of 17 variables were collected and subjected to univariate and multivariate prognostic factor analyses for OS.

[Clinical importance of retropharyngeal lymph node metastases].

Összefoglaló. A retropharyngealis nyirokcsomóáttétek incidenciája a primer fej-nyaki daganat lokalizációjától függ. Leggyakrabban az előrehaladott vagy recidív nasopharynx-carcinomák esetén fordul elő, de III-IV.

[Consequences of extracellular alterations of EGFR on cetuximab therapy in HNSCC].

Head and neck squamous cell carcinomas (HNSCC) take many lifes worldwide. Patients with recurrent/metastatic disease receive combination chemotherapy containing anti-EGFR antibody cetuximab. However, resistance often hurdles therapy.

Patritumab or placebo, with cetuximab plus platinum therapy in recurrent or metastatic squamous cell carcinoma of the head and neck: A randomised phase II study.

Background: The fully human monoclonal antibody patritumab blocks HER3 activation, a resistance mechanism to cetuximab, induced by heregulin (HRG). A phase Ib study in recurrent and/or metastatic (R/M) squamous cell carcinoma of the head and neck (SCCHN) demonstrated tolerability and tumour response of patritumab + cetuximab + platinum.

Methods: This was a randomised, double-blind, phase II study of patritumab + cetuximab with platinum-based therapy for first-line treatment of R/M SCCHN (Clinicaltrials.

Durvalumab for recurrent or metastatic head and neck squamous cell carcinoma: Results from a single-arm, phase II study in patients with ≥25% tumour cell PD-L1 expression who have progressed on platinum-based chemotherapy.

Background: Patients with recurrent/metastatic head and neck squamous cell carcinoma (R/M HNSCC) progressing on platinum-based chemotherapy have poor prognoses and limited therapeutic options. Programmed cell death-1 (PD-1) and its ligand 1 (PD-L1) are frequently upregulated in HNSCC. The international, multi-institutional, single-arm, phase II HAWK study (NCT02207530) evaluated durvalumab monotherapy, an anti-PD-L1 monoclonal antibody, in PD-L1-high patients with platinum-refractory R/M HNSCC.

Local immune parameters as potential predictive markers in head and neck squamous cell carcinoma patients receiving induction chemotherapy and cetuximab.

Background: The aim of this study was to determine whether tumor-associated immune cells may predict response to therapy and disease outcome in head and neck squamous cell carcinoma (HNSCC) patients receiving induction chemotherapy and cetuximab.

Methods: Paraffin-embedded pretreatment biopsy samples from 45 patients with stage III-IV resectable HNSCC were investigated retrospectively by immunohistochemistry for density of different immune cell types based on expression of CD8, FOXP3, CD134, CD137, PD-1, CD20, NKp46, dendritic cell lysosomal-associated membrane protein (DC-LAMP), CD16, CD68, and myeloperoxidase. Results were analyzed for possible correlations with clinicopathologic parameters, response to therapy, and survival.

Safety and Efficacy of Durvalumab With or Without Tremelimumab in Patients With PD-L1-Low/Negative Recurrent or Metastatic HNSCC: The Phase 2 CONDOR Randomized Clinical Trial.

Importance: Dual blockade of programmed death ligand 1 (PD-L1) and cytotoxic T-lymphocyte associated protein 4 (CTLA-4) may overcome immune checkpoint inhibition. It is unknown whether dual blockade can potentiate antitumor activity without compromising safety in patients with recurrent or metastatic head and neck squamous cell carcinoma (R/M HNSCC) and low or no PD-L1 tumor cell expression.

Objective: To assess safety and objective response rate of durvalumab combined with tremelimumab.

[First report on successful application of nivolumab in Hungary for the treatment of locally recurrent head and neck squamous cell carcinoma].

The prognosis for recurrent/metastatic head and neck squamous cell cancer (R/M HNSCC) remains dismal and its treatment poses a challenge for oncologists. Nivolumab belongs to the class of immune checkpoint inhibitors (ICI) and is an antibody developed to target the programmed cell death protein 1 (PD-1) receptor. The CheckMate 141 randomized phase 3 trial proved the efficacy of nivolumab in the treatment of R/M HNSCC as it was shown to significantly increase overall survival and quality of life.

[Role of MRI and CT in the evaluation of postirradiation status and complications in head and neck cancer].

Most head and neck cancer patients are treated with combined modalities such as surgery, radiotherapy (RT), chemotherapy (ChT). Concurrent chemo-radiation has improved treatment outcomes with increased toxic effects. Reactions after RT are divided into early and late changes.

[Retrospective analysis of papillary thyroid microcarcinoma cases treated between 2001 and 2010 in the Hungarian National Institute of Oncology].

The standard treatment of papillary microcarcinomas (mPTC; ≤1 cm) regardless of their size, was similar to the advanced ones till the recent past: immediate surgery ± radioactive iodine (RAI) therapy. However, the American Thyroid Association (ATA) 2015 guidelines accept the active surveillance in selected cases. We performed a retrospective analysis on the clinical data of 103 patients with PTmC in a single (62.

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

The preplanned exploratory analysis of the BERIL-1 trial presented here aimed to identify biomarkers of response to the combination of buparlisib and paclitaxel. BERIL-1 was a multicenter, randomized, double-blind, placebo-controlled phase II study. Patients with recurrent or metastatic squamous cell carcinoma of the head and neck (SCCHN) progressing on/after one previous platinum-based chemotherapy regimen in the recurrent or metastatic setting were treated with either buparlisib plus paclitaxel or placebo plus paclitaxel.

TPF plus cetuximab induction chemotherapy followed by biochemoradiation with weekly cetuximab plus weekly cisplatin or carboplatin: a randomized phase II EORTC trial.

Background: Our aim was to test the safety of cetuximab added to chemoradiation with either cisplatin or carboplatin after prior induction chemotherapy.

Methods: Patients with stage III/IV unresectable, squamous cell carcinoma of the head and neck received up to four cycles of TPF-E (cisplatin and docetaxel 75 mg/m2 on day 1 followed by 5-FU 750 mg/m2/day as a continuous infusion on days 1-5 plus cetuximab at a loading dose of 400 mg/m2 followed by a weekly dose of 250 mg/m2), with prophylactic antibiotics but no growth factors. Patients not progressing after four cycles of TPF-E were randomly assigned to radiotherapy (70 Gy over 7 weeks in 2 Gy fractions) and weekly cetuximab with either weekly cisplatin 40 mg/m2 or carboplatin, AUC of 1.

Evaluation of the impact of tumor HPV status on outcome in patients with locally advanced unresectable head and neck squamous cell carcinoma (HNSCC) receiving cisplatin, 5-fluorouracil with or without docetaxel: a subset analysis of EORTC 24971 study.

Background: EORTC 24971 was a phase III trial demonstrating superiority of induction regimen TPF (docetaxel, cisplatin, 5-fluorouracil) over PF (cisplatin/5-fluorouracil), in terms of progression-free (PFS) and overall survival (OS) in locoregionally advanced unresectable head and neck squamous cell carcinomas. We conducted a retrospective analysis of prospectively collected data aiming to evaluate whether only HPV(-) patients (pts) benefit from adding docetaxel to PF, in which case deintensifying induction treatment in HPV(+) pts could be considered.

Patients And Methods: Pretherapy tumor biopsies (blocks or slides) were assessed for high-risk HPV by p16 immunohistochemistry, PCR and quantitative PCR.

Buparlisib and paclitaxel in patients with platinum-pretreated recurrent or metastatic squamous cell carcinoma of the head and neck (BERIL-1): a randomised, double-blind, placebo-controlled phase 2 trial.

Background: Phosphatidylinositol 3-kinase (PI3K) pathway activation in squamous cell carcinoma of the head and neck contributes to treatment resistance and disease progression. Buparlisib, a pan-PI3K inhibitor, has shown preclinical antitumour activity and objective responses in patients with epithelial malignancies. We assessed whether the addition of buparlisib to paclitaxel improves clinical outcomes compared with paclitaxel and placebo in patients with recurrent or metastatic squamous cell carcinoma of the head and neck.

Impact of 3T multiparametric MRI and FDG-PET-CT in the evaluation of occult primary cancer with cervical node metastasis.

Background: This study aimed to determine the ability of multimodal evaluation with multiparametric 3T-MRI (MPMRI) and positron emission tomography - computed tomography (PET/CT) to detect cancer of unknown primary origin (CUP) with neck lymph node (LN) metastasis.

Methods: The study group comprised 38 retrospectively analysed consecutive patients with LN metastasis in the head and neck (HN) region without known primary tumours (PTs). Statistical values of 3T-MRI and of FDG-PET/CT scans were evaluated.

Docetaxel, cisplatin and 5-fluorouracil induction chemotherapy followed by chemoradiotherapy or chemoradiotherapy alone in stage III-IV unresectable head and neck cancer: Results of a randomized phase II study.

Purpose: Concurrent chemoradiotherapy (CRT) is the standard treatment for advanced head and neck squamous cell carcinoma. In this phase II randomized study, the efficacy and toxicity of docetaxel, cisplatin and 5-fluorouracil induction chemotherapy (ICT) followed by concurrent CRT was compared with those after standard CRT alone in patients with locally advanced, unresectable head and neck cancer.

Patients And Methods: Between January 2007 and June 2009, 66 patients with advanced (stage III or IV) unresectable squamous cell carcinoma of the head and neck (oral cavity, oropharynx, hypopharynx, and larynx) were randomly assigned to two groups: one receiving two cycles of docetaxel, cisplatin, and 5-fluorouracil ICT followed by CRT with three cycles of cisplatin and one treated by CRT alone.

Cisplatin, 5-fluorouracil, and cetuximab (PFE) with or without cilengitide in recurrent/metastatic squamous cell carcinoma of the head and neck: results of the randomized phase I/II ADVANTAGE trial (phase II part).

Background: Recurrent and/or metastatic squamous cell carcinoma of the head and neck (R/M-SCCHN) overexpresses αvβ5 integrin. Cilengitide selectively inhibits αvβ3 and αvβ5 integrins and is investigated as a treatment strategy.

Patients And Methods: The phase I/II study ADVANTAGE evaluated cilengitide combined with cisplatin, 5-fluorouracil, and cetuximab (PFE) in R/M-SCCHN.

Cetuximab and platinum-based chemoradio- or chemotherapy of patients with epidermal growth factor receptor expressing adenoid cystic carcinoma: a phase II trial.

Background: Epidermal growth factor receptor (EGFR) is highly expressed in adenoid cystic carcinoma (ACC). The efficacy and toxicity of cetuximab with concomitant platinum-based chemoradio- or chemotherapy in patients with locally advanced or metastatic ACC, respectively, was evaluated.

Methods: Eligible patients (9 with locally advanced tumour and 12 with metastases) had positive tumour EGFR expression.

[The role of PET-CT in detecting unknown primary tumour in patients with cervical lymph node metastases].

PET-CT examination was conducted with 440 patients treated at the Department of Head and Neck Surgery, National Institute of Oncology, Budapest, between January 1, 2006 and December 31, 2010. Out of them 77 patients were selected with whom no examination of any sort (physical, pan-endoscopy, or any of the conventional imaging techniques) succeeded in identifying the primary tumour. In each case the primary examination (aspiration cytology and histology) verified cervical metastases, most of them being squamous cell carcinoma.

Evaluation of EGFR gene copy number as a predictive biomarker for the efficacy of cetuximab in combination with chemotherapy in the first-line treatment of recurrent and/or metastatic squamous cell carcinoma of the head and neck: EXTREME study.

Background: The phase III EXTREME study demonstrated that combining cetuximab with platinum/5-fluorouracil (5-FU) significantly improved overall survival in the first-line treatment of patients with recurrent and/or metastatic squamous cell carcinoma of the head and neck (R/M SCCHN) compared with platinum/5-FU alone. The aim of this investigation was to evaluate elevated tumor EGFR gene copy number as a predictive biomarker in EXTREME study patients.

Patients And Methods: Dual-color FISH was used to determine absolute and relative EGFR copy number.

Short-term health-related quality of life and symptom control with docetaxel, cisplatin, 5-fluorouracil and cisplatin (TPF), 5-fluorouracil (PF) for induction in unresectable locoregionally advanced head and neck cancer patients (EORTC 24971/TAX 323).

Background: The EORTC 24971/TAX 323, a phase III study of 358 patients with unresectable locoregionally advanced squamous cell carcinoma of the head and neck, showed an improved progression-free and overall survival (OS) with less toxicity when docetaxel (T) was added to cisplatin and 5-fluorouracil (PF) for induction and given before radiotherapy (RT). The impact of the addition of docetaxel on patients' health-related quality of life (HRQOL) and symptoms was investigated.

Methods: HRQOL was assessed at baseline, at end of cycle 2, and 4, 6, and 9 months after completion of RT using the European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire C30 (QLQ-C30) and the EORTC QLQ Head and Neck Cancer-Specific Module (EORTC QLQ-H&N35).

[Cytogenetic and hormonal changes in head and neck squamous cell cancer patients: potential biomarkers for functional approaches in surgical oncology].

Squamous cell cancer of the head and neck (SCCHN) is the third most common cause of death from cancer among Hungarian males. This cancer is caused in most of the cases by chronic toxic effects of the environment, especially by tobacco smoking and regular alcohol consumption. SCCHNs similar for the first sight, might have different clinical course, mainly because of their different responses to anticancer therapies.