Understanding homologous recombination repair deficiency in biliary tract cancers: clinical implications and correlation with platinum sensitivity.

BACKGROUND: Biliary tract cancers (BTCs) exhibit high mortality rates and significant heterogeneity in both clinical and molecular characteristics. This study aims to molecularly characterize a cohort of patients with BTC, with a specific focus on genomic alterations within homologous recombination repair (HRR) genes in a real-world setting. PATIENTS AND METHODS: We carried out a retrospective analysis on 256 patients with BTC treated at five Austrian centers and one German comprehensive cancer center between 2016 and 2023 utilizing comprehensive genomic profiling platforms to assess HRR status and its correlation with clinical outcomes after platinum-based chemotherapy. RESULTS: A total of 67 patients (27.5%) exhibited HRR gene mutations (HRRm), with the most common pathogenic alterations in BAP1 (9%), ARID1A (7.8%), and ATM (6.1%). Time to failure of the first-line strategy (TFS) between patients with HRRm and non-HRRm treated with platinum agents was 7.9 and 6.7 months, respectively [hazard ratio (HR) 0.89; P = 0.49]. The overall survival (OS) estimates at 6, 18, and 24 months were 82%, 45%, and 39% in the HRRm group (median 16.01 months) and 81%, 42%, and 22% in the HRR group (median 15.68 months), respectively (Fleming-Harrington test P = 0.0004; log-rank P = 0.022). Significance did not persist in the multivariate analysis (HR 0.72; 95% confidence interval 0.489-1.059; P = 0.095). An interaction between HRRm status and molecular-informed therapeutic strategies in later lines was noted. In the second-line treatment, OS following an irinotecan-based regimen was comparable to re-exposure to platinum-based agents (12.36 versus 10.13 months; HR 0.92; P = 0.85). No better outcome was noted for patients with HRRm versus patients with non-HRRm with second-line platinum agents (HR 1.45; P = 0.35). CONCLUSIONS: Patients with HRRm with BTC showed a potential advantage in OS following platinum-based first-line chemotherapy, presumably attributed to enhanced opportunities for targetable coalterations. Further investigation is needed to outline HRR within the scope of BTCs and detail a clinically meaningful sensitivity to platinum agents or targeted approaches with poly (ADP-ribose) polymerase (PARP) inhibitors.

Efficacy of Listerine, Meridol and chlorhexidine mouthrinses on plaque, gingivitis and plaque bacteria vitality.

The experimental gingivitis model was used to compare the anti-plaque, anti-gingivitis and anti-microbial efficacies of a phenolic compound (Listerine) and an amine/stannous fluoride mouthwash (Meridol), using a placebo preparation as negative control and a chlorhexidine solution as positive control in a double-blind study. After professional toothcleaning, 36 volunteers performed optimal oral hygiene for a period of 2 weeks. They then ceased all oral hygiene procedures for 21 days during which they rinsed twice daily with 1 of the 4 mouthrinses. After 3 weeks of rinsing, plaque indices remained the lowest in the chlorhexidine group, while subjects using Listerine or Meridol harbored similar indices significantly lower than that of individuals rinsing with the placebo solution. Up to that time, the gingival index scores were equal in all groups except for the chlorhexidine group in which the values only amounted to half of these encountered in the other groups. The plaque vitality scores showed a bactericidal effect in vivo of chlorhexidine during the entire time of experimental gingivitis. In contrast, the data gave no evidence of an antibacterial effect in vivo of Listerine. The efficacy of Meridol to kill micro-organisms was similar to chlorhexidine during the early stages of plaque accumulation and, with time, became insignificant. This study has demonstrated that chlorhexidine was superior to Listerine and Meridol in its ability to maintain low plaque scores and gingival health during this 3-week period of no mechanical oral hygiene. Moreover, it was also shown that Meridol was as effective as Listerine in reducing plaque accumulation and, in contrast to Listerine, possessed a remarkable but transient antibacterial effect in vivo.