Study protocol of the FIRE-8 (AIO-KRK/YMO-0519) trial: a prospective, randomized, open-label, multicenter phase II trial investigating the efficacy of trifluridine/tipiracil plus panitumumab versus trifluridine/tipiracil plus bevacizumab as first-line treatment in patients with metastatic colorectal cancer.

BACKGROUND: Initial systemic therapy for patients with metastatic colorectal cancer (mCRC) is usually based on two- or three-drug chemotherapy regimens with fluoropyrimidine (5-fluorouracil (5-FU) or capecitabine), oxaliplatin and/or irinotecan, combined with either anti-VEGF (bevacizumab) or, for RAS wild-type (WT) tumors, anti-EGFR antibodies (panitumumab or cetuximab). Recommendations for patients who are not eligible for intensive combination therapies are limited and include fluoropyrimidine plus bevacizumab or single agent anti-EGFR antibody treatment. The use of a monochemotherapy concept of trifluridine/ tipiracil in combination with monoclonal antibodies is not approved for first-line therapy, yet. Results from the phase II TASCO trial evaluating trifluridine/ tipiracil plus bevacicumab in first-line treatment of mCRC patients and from the phase I/II APOLLON trial investigating trifluridine/ tipiracil plus panitumumab in pre-treated mCRC patients suggest favourable activity and tolerability of these new therapeutic approaches. METHODS: FIRE-8 ( NCT05007132 ) is a prospective, randomized, open-label, multicenter phase II study which aims to evaluate the efficacy of first-line treatment with trifluridine/tipiracil (35 mg/m2 body surface area (BSA), orally twice daily on days 1-5 and 8-12, q28 days) plus either the anti-EGFR antibody panitumumab (6 mg/kg body weight, intravenously on day 1 and 15, q28 days) [arm A] or (as control arm) the anti-VEGF antibody bevacizumab (5 mg/kg body weight, intravenously on day 1 and 15, q28 days) [arm B] in RAS WT mCRC patients. The primary objective is to demonstrate an improved objective response rate (ORR) according to RECIST 1.1 from 30% (control arm) to 55% with panitumumab. With a power of 80% and a two-sided significance level of 0.05, 138 evaluable patients are needed. Given an estimated drop-out rate of 10%, 153 patients will be enrolled. DISCUSSION: To the best of our knowledge, this is the first phase II trial to evaluate the efficacy of trifluridine/tipiracil plus panitumumab in first-line treatment of RAS WT mCRC patients. The administration of anti-EGFR antibodies rather than anti-VEGF antibodies in combination with trifluridine/tipiracil may result in an increased initial efficacy. TRIAL REGISTRATION: EU Clinical Trials Register (EudraCT) 2019-004223-20 . Registered October 22, 2019, ClinicalTrials.gov NCT05007132 . Registered on August 12, 2021.

Pulp calcifications in traumatized primary incisors. A morphological and inductive analysis study.

The purpose of this study was to investigate histopathological changes in primary teeth following trauma, and to look for possible correlations between the morphology of pulpal calcification and clinical findings. The material consisted of 123 primary teeth from 98 Danish children aged 9-108 months (mean age 33.5 +/- 19.7 months) at the time of injury. The specimens were analyzed by means of light and scanning and transmission electron microscopy. Data from the clinical investigation and from predetermined ranked parameters from the histological analysis were processed in a computerized inductive analysis program. The results, describing patterns of co-variation, are presented as a decision tree. The most common diagnosis was intrusion luxation (54%). In 41% of all teeth, the degree of obliteration was less than 1/4 of the pulpal lumen. In most cases (79%), no denticles were visible. When present, 80% of the denticles had a bone-like appearance. Tissues occluding the pulpal lumen were either dentin-like (49%), bone-like (19%), or fibrotic (9%). It could be concluded that these varying responses could not be correlated with explicit clinical diagnoses. However, in certain combinations, histological parameters could be correlated to clinical findings.

[Clinical and microstructural comparative studies on fillings made from gallium-tin-nickel alloys and from silver-tin amalgam]. / Klinische und mikrostrukturelle Vergleichsuntersuchungen an Füllungen aus Gallium-Zinn-Nickel-Legierungen und Silber-Zinn-Amalgam.

The filling material "Gallodent" has been clinically controlled for a period of one year. Scanning electron microscopic examinnations revealed greater surface porosity with negligible microleakage and better marginal adaptation as compared to amalgam. Early corrosion phenomena required re-polishing every three months. This disadvantage and the brittleness of the gallium-tin-nickel alloys hinder, at present, these alloys from superseding high-silver amalgams.