BACKGROUND: Most head and neck squamous-cell carcinomas (HNSCCs) are driven by p16 inactivation and cyclin D1 overexpression that results in hyperactivation of cyclin-dependent kinase 4 and 6 (CDK4/6), rather than by the human papillomavirus (HPV). Deregulated cyclin D1 expression also causes resistance to EGFR inhibitors. We previously reported that palbociclib (a selective CDK4/6 inhibitor) given with cetuximab (an EGFR inhibitor) was safe. The aim of this study was to establish the proportion of patients achieving an objective response with palbociclib and cetuximab in recurrent or metastatic HNSCC.

METHODS: We did a multicentre, multigroup, phase 2 trial to evaluate the activity of palbociclib and cetuximab in platinum-resistant (group 1) and cetuximab-resistant (group 2) HPV-unrelated HNSCC. The study was done across eight university sites in the USA. Eligibility required measurable disease (according to Response Evaluation Criteria in Solid Tumors, version 1·1 [RECIST 1·1]), Eastern Cooperative Oncology Group (ECOG) performance status of 0-2, age of 18 years or older, and disease progression on platinum but cetuximab-naive (group 1) or disease progression on cetuximab (group 2). All patients received palbociclib orally (125 mg/day, on days 1-21) and intravenous cetuximab (400 mg/m on cycle one, day 1, then 250 mg/m once per week) in 28-day cycles. The primary endpoint was objective response (complete responses and partial responses per RECIST 1·1). Analyses were done per protocol. This trial was registered with ClinicalTrials.gov, NCT02101034, and is ongoing, but both groups are closed to accrual.

FINDINGS: Between Oct 19, 2015, and Nov 7, 2018, 62 patients were enrolled onto the trial: 30 patients were enrolled in group 1 and 32 in group 2. Median follow-up was 5·4 months (IQR 4·4-12·1) for group 1 and 5·5 months (4·3-8·3) for group 2. In group 1, of 28 evaluable patients, an objective response was achieved by 11 (39%; 95% CI 22-59). In group 2, of 27 evaluable patients, an objective response was achieved by five (19%; 6-38) in group 2. The most common grade 3-4 palbociclib-related adverse event was neutropenia (in 21 [34%] of 62 patients). No treatment-related deaths occurred.

INTERPRETATION: In patients with platinum-resistant or cetuximab-resistant HPV-unrelated HNSCC, palbociclib and cetuximab results in promising activity outcomes. Further studies of CDK4/6 inhibitors are warranted in HPV-unrelated HNSCC.

FUNDING: Pfizer.

OBJECTIVE: The treatment of nasopharyngeal stenosis is challenging because of a high incidence of recurrence after surgical correction. Therefore, many treatment modalities are being tried to cure this problem. The aim of this study is to assess the efficacy of palatal eversion as a new technique for treatment of nasopharyngeal stenosis after adenotonsillectomy.

STUDY DESIGN: Case series.

METHODS: This study was conducted on 12 patients with nasopharyngeal stenosis after adenotonsillectomy were subjected to treatment by palatal eversion by dividing the soft palate in the midline and removal of the fibrous tissue causing stenosis followed by evertion and fixation of the two palatal division on either side for six weeks to allow complete epithelialization of the stenotic area followed by another operation to reunion the soft palate in the midline. Post-operative follow up was done for one year by flexible nasopharyngoscopy, perceptual speech analysis and polysomnography.

RESULTS: Flexible nasopharyngosopic examination of the 12 patients at the end of post-operative period revealed a freely mobile soft palate with no nasopharyngeal stenosis or palatal fistula. Velopharyngeal function and speech assessment by perceptual speech analysis was normal in all 12 cases. No obstructive episodes were recorded in polysomnograms.

CONCLUSIONS: Palatal eversion is a promising technique in treatment of post-adenotonsillectomy nasopharyngeal stenosis and it is recommended to be used in a wider scale of patients and other indications as nasopharyngeal stenosis following uvulopalatoplasty and post nasopharyngeal radiotherapy.

LEVEL OF EVIDENCE: 4 (case series).

OBJECTIVE: Rarely the tonsillar pillars and the soft palate became adherent to the posterior nasopharyngeal wall by strong fibrous tissue due to excessive dissection and cauterization during surgery leading to nasopharyngeal stenosis. Therefore, many treatment modalities are being tried to cure this problem. The aim of this study is to explore our results of modifying the basic technique to accommodate those patients with combined nasopharyngeal stenosis and tonsillar pillars adhesions in one stage.

STUDY DESIGN: Case series.

METHODS: This study was conducted on 10 patients with combined nasopharyngeal stenosis and tonsillar pillars adhesions after adenotonsillectomy. They were subjected to treatment by palatal eversion through dividing the soft palate in the midline to separate each pillar from the pharyngeal wall in continuation with each half of soft palate and removal of the fibrous tissue causing stenosis. This was followed by eversion and fixation of the two palatal divisions on either side to allow complete epithelialization of the stenotic area. Postoperative follow-up was done for one year by the flexible nasopharyngoscopy, perceptual speech analysis, and polysomnography.

RESULTS: The flexible nasopharyngosopic examination of the 10 patients at the end of post-operative period revealed a freely mobile soft palate with no nasopharyngeal stenosis or palatal fistula. Velopharyngeal function and speech assessment by perceptual speech analysis was normal in all 10 cases. No obstructive episodes were recorded in polysomnograms.

CONCLUSIONS: Palatal eversion is a promising technique in the treatment of post-adenotonsillectomy of combined nasopharyngeal stenosis and tonsillar pillars adhesion. It is recommended to be used on a wider scale of patients and other indications as nasopharyngeal stenosis following uvulopalatoplasty and post nasopharyngeal radiotherapy. The level of evidence: 4 (case series).

This study analyzed cone beam computed tomography (CBCT) records. Radiographic image analysis included: (1) the width and height of the palatal vault, and diameter and location of the incisive foramen; (2) the potential block graft dimensions and their correlation to arch dimensions; (3) the potential graft size and its variation by sex. CBCT scans of 76 patients were included, 42 from female patients and 34 from male patients (mean age 42.3 years). The mean palatal width was 35.2±3.4 mm, while the mean palatal height was 15.2±2.9 mm. The mean diameter of the incisive foramen was 3.1±1.3. mm. The mean potential osteotomy diameter was 7.8±1.5 mm. The mean osteotomy length varied according to site: central incisor region, 5.9±2.0 mm; lateral incisor region, 5.2±2.1 mm; canine region, 4.7±1.9 mm; premolar region, 4.1±1.7 mm. A positive correlation was observed between the osteotomy diameter and the palatal width: a greater osteotomy length was obtained from the more anterior teeth position. Males presented significantly greater osteotomy diameter and length compared to females. The palate represents a potential site for the harvest of autogenous bone block grafts for the reconstruction of ridge defects.

Pairwise global sequence alignment is a vital process for finding functional and evolutionary similarity between biological sequences. The main usage of it is searching biological databases for finding the origin of unknown sequence. The standard global alignment based on dynamic programming approach which produces the accurate alignment but with extensive execution time. In this paper, Sine-Cosine optimization algorithm was used for accelerating pairwise global alignment with alignment score near one produced by dynamic programming alignment. The reason for using Sine-Cosine optimization is its excellent exploration of the search space. The developed technique was tested on human and mouse protein sequences and its success for finding alignment similarity 75% of that produced by standard technique.