Assessment of targeted therapy opportunities in sinonasal cancers using patient-derived functional tumor models.

Malignant tumors derived from the epithelium lining the nasal cavity region are termed sinonasal cancers, a highly heterogeneous group of rare tumors accounting for 3 - 5 % of all head and neck cancers. Progress with next-generation molecular profiling has improved our understanding of the complexity of sinonasal cancers and resulted in the identification of an increasing number of distinct tumor entities. Despite these significant developments, the treatment of sinonasal cancers has hardly evolved since the 1980s, and an advanced sinonasal cancer presents a poor prognosis as targeted therapies are usually not available. To gain insights into potential targeted therapeutic opportunities, we performed a multiomics profiling of patient-derived functional tumor models to identify molecular characteristics associated with pharmacological responses in the different subtypes of sinonasal cancer. METHODS: Patient-derived ex vivo tumor models representing four distinct sinonasal cancer subtypes: sinonasal intestinal-type adenocarcinoma, sinonasal neuroendocrine carcinoma, sinonasal undifferentiated carcinoma and SMARCB1 deficient sinonasal carcinoma were included in the analyses. Results of functional drug screens of 160 anti-cancer therapies were integrated with gene panel sequencing and histological analyses of the tumor tissues and the ex vivo cell cultures to establish associations between drug sensitivity and molecular characteristics including driver mutations. RESULTS: The different sinonasal cancer subtypes display considerable differential drug sensitivity. Underlying the drug sensitivity profiles, each subtype was associated with unique molecular features. The therapeutic vulnerabilities correlating with specific genomic background were extended and validated with in silico analyses of cancer cell lines representing different human cancers and with reported case studies of sinonasal cancers treated with targeted therapies. CONCLUSION: The results demonstrate the importance of understanding the differential biology and the molecular features associated with the different subtypes of sinonasal cancers. Patient-derived ex vivo tumor models can be a powerful tool for investigating these rare cancers and prioritizing targeted therapeutic strategies for future clinical development and personalized medicine.

LUPP relieves partial upper airway obstruction during sleep in patients with velopharyngeal narrowing.

CONCLUSION: Patients with upper airway narrowing at the soft palate level and partial upper airway obstruction during sleep seem to benefit from laser-assisted uvulopalatoplasty (LUPP) in terms of decreased velopharyngeal collapsibility and improved nocturnal breathing. OBJECTIVES: The current operative treatments for obstructive sleep apnea syndrome (OSAS) are not very effective compared with continuous positive airway pressure (CPAP). It has been suggested that active treatment should be performed earlier, when sleep apnea is present in a milder form. The main problem is identifying progressive sleep apnea. The present study assessed the efficacy of LUPP in patients with partial upper airway obstruction during sleep diagnosed by means of a static charge-sensitive bed (SCSB) combined with oxyhemoglobin desaturation recording and digital fluoroscopy-based collapsibility estimation. METHODS: LUPP was carried out in 27 patients under local anesthesia as day surgery. Digital fluoroscopy and SCSB were recorded preoperatively and 6 months after LUPP. RESULTS: Partial upper airway obstruction events and arterial oxyhemoglobin desaturations during sleep decreased significantly. Digital fluoroscopy revealed that the minimal anteroposterior dimension increased and collapsibility decreased at the level where velopharyngeal obstruction occurred, the soft palate.

Uvulopalatopharyngoplasty with an ultrasound scalpel or laser: is there a difference?

Uvulopalatopharyngoplasty (UPPP) is used for treatment of the obstructive sleep apnoea syndrome, mainly in the lower range of the apnoea-hypopnea index or partial upper airway obstruction. Significant severe pain after UPPP is associated in the area having surgery and therefore less pain causing methods should be investigated. In this study, we compared laser-assisted and ultrasound scalpel-performed UPPP. Sleep apnoea patients (n = 40) recruited to the study were divided into two groups. UPPP was performed with either laser-assisted or an ultrasound scalpel. Perioperative bleeding, operating room time and duration of operation together with histological injury of soft palate were analysed. A postoperative follow-up questionnaire included a self analysis of pain, dietary intake and pain drug consumption. In the same follow-up form, filled in by patients themselves, possible side effects and adequacy of pain medication together with any postoperative haemorrhage events were recorded during 10-day study period after UPPP. The ultrasound scalpel group had significantly fewer haemorrhagic events (P = 0.037) during postoperative follow-up time after UPPP when compared to laser-assisted group. The pain values of all 40 patients were significantly higher in the morning than in the afternoon (P < 0.001) or evening (P < 0.001). Pain increased up to the fifth postoperative day (visual analogue scale, VAS = 46). The significant relief of pain to the mild level (VAS < 30 mm) occurred at ninth and tenth postoperative day. The ultrasound scalpel used as a surgical method in UPPP did not offer significant comprehensive benefits in this study compared to laser-assisted UPPP. Exclusively, postoperative haemorrhage events were minor, paralleling findings of previous studies where ultrasound scalpel had been used for tonsillectomy. We conclude that the ultrasound scalpel is comparable to laser-assisted UPPP.