Oral cancer prediction by noninvasive genetic screening

Oral squamous cell carcinomas (OSCCs) develop in genetically altered epithelium in the mucosal lining, also coined as fields, which are mostly not visible but occasionally present as white oral leukoplakia (OL) lesions. We developed a noninvasive genetic assay using next-generation sequencing (NGS) on brushed cells to detect the presence of genetically altered fields, including those that are not macroscopically visible. The assay demonstrated high accuracy in OL patients when brush samples were compared with biopsies as gold standard. In a cohort of Fanconi anemia patients, detection of mutations in prospectively collected oral brushes predicted oral cancer also when visible abnormalities were absent. We further provide insight in the molecular landscape of OL with frequent changes of TP53, FAT1 and NOTCH1. NGS analysis of noninvasively collected samples offers a highly accurate method to detect genetically altered fields in the oral cavity, and predicts development of OSCC in high-risk individuals. Noninvasive genetic screening can be employed to screen high-risk populations for cancer and precancer, map the extension of OL lesions beyond what is visible, map the oral cavity for precancerous changes even when visible abnormalities are absent, test accuracy of promising imaging modalities, monitor interventions and determine genetic progression as well as the natural history of the disease in the human patient.     

Effect of root perforation repair with mineral aggregate-based cements on the retention of customized fiberglass posts

Odontology - The purpose of this study was to investigate whether the root perforation repair with mineral aggregate-based cements affects the retention of customized fiberglass posts to bovine...     

Limited clinical activity of palbociclib and ribociclib monotherapy in advanced cancers with cyclin D-CDK4/6 pathway alterations in the Dutch DRUP and Australian MoST trials

The Dutch Drug Rediscovery Protocol (DRUP) and the Australian Cancer Molecular Screening and Therapeutic (MoST) Program are similar nonrandomized, multidrug, pan-cancer trial platforms that aim to identify signals of clinical activity of molecularly matched targeted therapies or immunotherapies outside their approved indications. Here, we report results for advanced or metastatic cancer patients with tumors harboring cyclin D-CDK4/6 pathway alterations treated with CDK4/6 inhibitors palbociclib or ribociclib. We included adult patients that had therapy-refractory solid malignancies with the following alterations: amplifications of CDK4, CDK6, CCND1, CCND2 or CCND3, or complete loss of CDKN2A or SMARCA4. Within MoST, all patients were treated with palbociclib, whereas in DRUP, palbociclib and ribociclib were assigned to different cohorts (defined by tumor type and alteration). The primary endpoint for this combined analysis was clinical benefit, defined as confirmed objective response or stable disease ≥16 weeks. We treated 139 patients with a broad variety of tumor types; 116 with palbociclib and 23 with ribociclib. In 112 evaluable patients, the objective response rate was 0% and clinical benefit rate at 16 weeks was 15%. Median progression-free survival was 4 months (95% CI: 3-5 months), and median overall survival 5 months (95% CI: 4-6 months). In conclusion, only limited clinical activity of palbociclib and ribociclib monotherapy in patients with pretreated cancers harboring cyclin D-CDK4/6 pathway alterations was observed. Our findings indicate that monotherapy use of palbociclib or ribociclib is not recommended and that merging data of two similar precision oncology trials is feasible.     

Use and Applicability of the Gail Model to Calculate Breast Cancer Risk: A Scoping Review

Objective: To perform a scoping review of the applicability of the Gail model in different countries for different ethnicities. Methods: The review was conducted based on the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews (PRISMA-ScR) checklist and search strategies based on the PICOS approach. The reviewed articles were included if they were published between 2013 and 2018 in English, Portuguese, or Spanish; were original articles available in full online; and described the use of the Gail model. The PubMed, Embase, and Web of Science data bases were searched. Results: A total of 38 articles eligible for analysis were identified, of which 16 used the Gail model to assess breast cancer risk in women, eight analyzed the applicability of this tool in their population, seven compared the tool and/or modified it according to the specific risk factors of their population, and seven cited the model in determining eligibility for chemoprevention. Conclusion: The Gail model has different applicabilities Greater effectiveness and breast cancer risk are found in developed countries.     

Drezotomía en el tratamiento del dolor por desaferentización: revisión de resultados y análisis de factores predictores de éxito

Background and objectivesThe treatment of deafferentation pain by spinal DREZotomy is a proven therapeutic option in the literature. In recent years, use of DREZotomy has been relegated to second place due to the emergence of neuromodulation therapies. The objectives of this study are to demonstrate that DREZotomy continues to be an effective and safe treatment and to analyse predictive factors for success.Patients and methodsA retrospective study was conducted of all patients treated in our department with spinal DREZotomy from 1998 to 2018. Bulbar DREZotomy procedures were excluded. A visual analogue scale (VAS) and the reduction of routine medication were used as outcome variables. Demographic, clinical and operative variables were analysed as predictive factors for success.ResultsA total of 27 patients (51.9% female) with a mean age of 53.7 years underwent DREZotomy. The main cause of pain was brachial plexus injury (BPI) (55.6%) followed by neoplasms (18.5%). The mean time of pain evolution was 8.4 years with a mean intensity of 8.7 according to the VAS, even though 63% of the patients had previously received neurostimulation therapy. Favourable outcome (≥ 50% pain reduction in the VAS) was observed in 77.8% of patients during the postoperative period and remained in 59.3% of patients after 22 months average follow-up (mean reduction of 4.9 points). This allowed for a reduction in routine analgesic treatment in 70.4% of them. DREZotomy in BPI-related pain presented a significantly higher success rate (93%) than the other pathologies (41.7%) (p = .001). No association was observed between outcome and age, gender, DREZ technique, duration of pain or previous neurostimulation therapies. There were six neurological complications, four post-operative transient neurological deficits and two permanent deficits.ConclusionDorsal root entry zone surgery is effective and safe for treating patients with deafferentation pain, especially after brachial plexus injury. It can be considered an alternative treatment after failed neurostimulation techniques for pain control. However, its indication should be considered as the first therapeutic option after medical therapy failure due to its good long-term results.