Phase II trial of domatinostat (4SC-202) in combination with avelumab in patients with previously treated advanced mismatch repair proficient oesophagogastric and colorectal adenocarcinoma: EMERGE.

BACKGROUND: Most oesophagogastric adenocarcinomas (OGAs) and colorectal cancers (CRCs) are mismatch repair proficient (MMRp), responding poorly to immune checkpoint inhibition. We evaluated the safety and efficacy of domatinostat (histone deacetylase inhibitor) plus avelumab (anti-PD-L1 antibody) in patients with previously treated inoperable, advanced/metastatic MMRp OGA and CRC. PATIENTS AND METHODS: Eligible patients were evaluated in a multicentre, open-label dose escalation/dose expansion phase II trial. In the escalation phase, patients received escalating doses of domatinostat [100 mg once daily (OD), 200 mg OD, 200 mg twice daily (BD)] orally for 14 days followed by continuous dosing plus avelumab 10 mg/kg administered intravenously 2-weekly (2qw) to determine the recommended phase II dose (RP2D). The trial expansion phase evaluated the best objective response rate (ORR) during 6 months by RECIST version 1.1 using a Simon two-stage optimal design with 2/9 and 1/10 responses required to proceed to stage 2 in the OGA and CRC cohorts, respectively. RESULTS: Patients (n = 40) were registered between February 2019 and October 2021. Patients in the dose escalation phase (n = 12) were evaluated to confirm the RP2D of domatinostat 200 mg BD plus avelumab 10 mg/kg. No dose-limiting toxicities were observed. Twenty-one patients were treated at the RP2D, 19 (9 OGA and 10 CRC) were assessable for the best ORR; 2 patients with CRC did not receive combination treatment and were not assessable for the primary endpoint analysis. Six patients were evaluated in the dose escalation and expansion phases. In the OGA cohort, the best ORR was 22.2% (95% one-sided confidence interval lower bound 4.1) and the median duration of disease control was 11.3 months (range 9.9-12.7 months). No responses were observed in the CRC cohort. No treatment-related grade 3-4 adverse events were reported at the RP2D. CONCLUSIONS: Responses in the OGA cohort met the criteria to expand to stage 2 of recruitment with an acceptable safety profile. There was insufficient signal in the CRC cohort to progress to stage 2. TRIAL REGISTRATION: NCT03812796 (registered 23rd January 2019).

Preventive treatment of post-traumatic dental infraocclusion: study on the knowledge of dental decoronation in a sample of Italian dental students and dentists.

AIM: The aim of the present work is to investigate whether dental decoronation is a procedure known by a sample of dental students and Italian dentists. Dental decoronation technique is performed in order to mitigate the outcomes which may occur after a delayed tooth replantation. MATERIALS AND METHODS: A cognitive survey about the knowledge of the dental decoronation technique was carried on two groups: a sample of 120 dental students (5th year of dental school), from University of Cagliari, Sassari and of Chieti-Pescara (60 males and 60 females), and a group which involved 200 Italian dentists (age comprised between 25 and 45, 130 females and 70 males) enrolled at pedodontics and orthodontics Masters and CE courses (University of Roma Sapienza, Chieti- Pescara, Cagliari). The latter group's main field of work was paediatric dentistry and orthodontics, two dental specialties often involved in treating Traumatic dental injuries. RESULTS: Only 20 dentists out of the 200 interviewed answered that they knew this technique and only 5 of them proved to know it and were able to describe it correctly. No students interviewed knew this technique. CONCLUSION: It is apparent from the results of this survey that there is very little information about the dental decoronation technique both during the Degree Course in Dentistry and Post Graduate specialty programmes (Continuing Education Courses and Masters).

Use of mouth guard in basketball: observational study of a group of teenagers with and without motivational reinforcement.

AIM: This study aims at ascertaining the capacity of 2 groups of young athletes to be faithful to the initial oral prevention project, with the difference that the study group received motivational reminders by either researchers and technical staff members of the team during the observation period, while the control group did not receive any motivational reminders. MATERIALS AND METHODS: This observational study was based on two groups selected from a wide group of 150 adolescent basketball players who accepted to use a custom-made mouth guard during their sport sessions. None of the selected athletes (60 adolescents aged between 12 and 15 years) had ever worn a mouth guard during their sports activity. A customised mouth guard was supplied, and subjetcs were requested to wear it for 12 months during training sessions and competitions. The study group was composed of 30 athletes, 15 males and 15 females, who received a constant motivational reinforcement to the use of the mouth guard by their coach and during checkups. Similarly, the control group was composed of 30 athletes (15 males and 15 females) who did not receive any motivational reinforcement. RESULTS: Twelve months after the beginning of the study, 24 subjects belonging to the control group were not using the mouth guard, while only 7 subjects of the study group were not using it. It was also noticed, six months after the beginning of the observation period, a rapid decline in the participants' interest in the use of the mouth guard. CONCLUSION: No traumatic event was registered among those adolescents who had used the mouth guard for the whole period of the study. Female athletes showed greater compliance to this prevention project. It is important that all technical staff members, and particularly the leading coach, encourage the regular use of oral protection devices for prevention among teenagers practicing sports.

Second cancer risk and mortality in men treated with radiotherapy for stage I seminoma.

BACKGROUND: Patients with stage I testicular seminoma are typically diagnosed at a young age and treatment is associated with low relapse and mortality rates. The long-term risks of adjuvant radiotherapy in this patient group are therefore particularly relevant. METHODS: We identified patients and obtained treatment details from 12 cancer centres (11 United Kingdom, 1 Norway) and ascertained second cancers and mortality through national registries. Data from 2629 seminoma patients treated with radiotherapy between 1960 and 1992 were available, contributing 51,151 person-years of follow-up. RESULTS: Four hundred and sixty-eight second cancers (excluding non-melanoma skin cancers) were identified. The standardised incidence ratio (SIR) was 1.61 (95% confidence interval (CI): 1.47-1.76, P<0.0001). The SIR was 1.53 (95% CI: 1.39-1.68, P<0.0001) when the 32 second testicular cancers were also excluded. This increase was largely due to an excess risk to organs in the radiation field; for pelvic-abdominal sites the SIR was 1.62 (95% CI: 1.43-1.83), with no significant elevated risk of cancers in organs elsewhere. There was no overall increase in mortality with a standardised mortality ratio (SMR) of 1.06 (95% CI: 0.98-1.14), despite an increase in the cancer-specific mortality (excluding testicular cancer deaths) SMR of 1.46 (95% CI: 1.30-1.65, P<0.0001). CONCLUSION: The prognosis of stage I seminoma is excellent and it is important to avoid conferring long-term increased risk of iatrogenic disease such as radiation-associated second cancers.

Prosthetic rehabilitation interventions in adolescents with fixed bridges: a 5-year observational study.

AIM: The aim of this work is to verify the rate of success and failure causes of 32 FRC-FPD (Fiber Reinforced Composite Fixed Partial Dentures) placed on 30 adolescents with dental agenesis, over a follow-up period of 5 years. MATERIALS AND METHODS: Our study sample involved 30 subjects (10 males and 20 females) aged between 13 and 17 years who have been rehabilitated with FRC Maryland bridges to treat agenesis of maxillary incisors (for a total of 32 FRC-FPD). The observational study spans 5 years following the general rules coded by the modified United States Public Health Service (USPHS) system. RESULTS: After 5 years of follow-up of a sample of 32 FRC-FPD bridges, 30 were still in effective use (so 2 were excluded). All the bridges were FRC, replacing a missing lateral incisor, and had a double wing retention. All requirements of stability, peripheral seal and morphology preservation were well satisfied. The two failed bridges had a structural failure after about two years from placement. DISCUSSION AND CONCLUSION: In adolescents our orientation about the edentulous rehabilitation is towards solutions that, when possible, provide an acceptable aesthetic and functional restoration with fixed partial dentures, or removable dentures in cases of severe oligodontia. Obviously, techniques involving the placement of dental implants before the end of skeletal growth were never adopted. In our study FRC bridges showed a great functional performance and good compliance from young patients. Considering the positive cost-benefit ratio and the reversibility of the treatment in case of failure, such interventions can be considered a highly reliable early rehabilitation. Further studies are necessary to verify the maintenance requirements tested for longer periods.