Bevacizumab, Irinotecan, or Topotecan Added to Temozolomide for Children With Relapsed and Refractory Neuroblastoma: Results of the ITCC-SIOPEN BEACON-Neuroblastoma Trial

\ua9 2024 by American Society of Clinical Oncology.PURPOSE Outcomes for children with relapsed and refractory high-risk neuroblastoma (RR-HRNB) remain dismal. The BEACON Neuroblastoma trial (EudraCT 2012-000072-42) evaluated three backbone chemotherapy regimens and the addition of the antiangiogenic agent bevacizumab (B). MATERIALS Patients age 1-21 years with RR-HRNB with adequate organ function and AND METHODS performance status were randomly assigned in a 3 3 2 factorial design to temozolomide (T), irinotecan-temozolomide (IT), or topotecan-temozolomide (TTo) with or without B. The primary end point was best overall response (complete or partial) rate (ORR) during the first six courses, by RECIST or International Neuroblastoma Response Criteria for patients with measurable or evaluable disease, respectively. Safety, progression-free survival (PFS), and overall survival (OS) time were secondary end points. RESULTS One hundred sixty patients with RR-HRNB were included. For B random assignment (n 5 160), the ORR was 26% (95% CI, 17 to 37) with B and 18% (95% CI, 10 to 28) without B (risk ratio [RR], 1.52 [95% CI, 0.83 to 2.77]; P 5 .17). Adjusted hazard ratio for PFS and OS were 0.89 (95% CI, 0.63 to 1.27) and 1.01 (95% CI, 0.70 to 1.45), respectively. For irinotecan ([I]; n 5 121) and topotecan (n 5 60) random assignments, RRs for ORR were 0.94 and 1.22, respectively. A potential interaction between I and B was identified. For patients in the bevacizumab-irinotecan-temozolomide (BIT) arm, the ORR was 23% (95% CI, 10 to 42), and the 1-year PFS estimate was 0.67 (95% CI, 0.47 to 0.80). CONCLUSION The addition of B met protocol-defined success criteria for ORR and appeared to improve PFS. Within this phase II trial, BIT showed signals of antitumor activity with acceptable tolerability. Future trials will confirm these results in the chemoimmunotherapy era

Bevacizumab, Irinotecan, or Topotecan Added to Temozolomide for Children With Relapsed and Refractory Neuroblastoma: Results of the ITCC-SIOPEN BEACON-Neuroblastoma Trial

Purpose Outcomes for children with relapsed and refractory high-risk neuroblastoma (RR-HRNB) remain dismal. The BEACON Neuroblastoma trial (EudraCT 2012-000072-42) evaluated three backbone chemotherapy regimens and the addition of the antiangiogenic agent bevacizumab (B). Materials and Methods Patients age 1-21 years with RR-HRNB with adequate organ function and performance status were randomly assigned in a 3 × 2 factorial design to temozolomide (T), irinotecan-temozolomide (IT), or topotecan-temozolomide (TTo) with or without B. The primary end point was best overall response (complete or partial) rate (ORR) during the first six courses, by RECIST or International Neuroblastoma Response Criteria for patients with measurable or evaluable disease, respectively. Safety, progression-free survival (PFS), and overall survival (OS) time were secondary end points. Results One hundred sixty patients with RR-HRNB were included. For B random assignment (n = 160), the ORR was 26% (95% CI, 17 to 37) with B and 18% (95% CI, 10 to 28) without B (risk ratio [RR], 1.52 [95% CI, 0.83 to 2.77]; P = .17). Adjusted hazard ratio for PFS and OS were 0.89 (95% CI, 0.63 to 1.27) and 1.01 (95% CI, 0.70 to 1.45), respectively. For irinotecan ([I]; n = 121) and topotecan (n = 60) random assignments, RRs for ORR were 0.94 and 1.22, respectively. A potential interaction between I and B was identified. For patients in the bevacizumab-irinotecan-temozolomide (BIT) arm, the ORR was 23% (95% CI, 10 to 42), and the 1-year PFS estimate was 0.67 (95% CI, 0.47 to 0.80). Conclusion The addition of B met protocol-defined success criteria for ORR and appeared to improve PFS. Within this phase II trial, BIT showed signals of antitumor activity with acceptable tolerability. Future trials will confirm these results in the chemoimmunotherapy era

Efficacy of simulation-based training on transoesophageal echocardiography learning in a multicentre randomised controlled trial: SIMULATOR study

Background Evidence on the impact of simulation-based training in transesophageal echocardiography (TEE) is scarce. Purpose We aimed to assess the efficacy of simulation-based versus traditional teaching on TEE knowledge and skills for cardiology residents. Methods Between November 2020 and November 2021, all consecutive cardiology residents inexperienced from TEE were randomised (1:1, n=324) through 42 French University Centers into two groups with or without simulation support (either a simulation group or a traditional group). The coprimary outcomes were the scores in the final theoretical and practical tests 3 months after the training. TEE duration and the feelings of residents were also assessed. An economic analysis was also performed. Results While the theoretical and practical test scores were similar between the two groups before the training (respectively P=0.80 and P=0.51), the residents in the simulation group displayed higher theoretical test and practical test scores after the training than those in the traditional group (respectively 47.2±15.6% vs. 38.3±19.8%, P<0.0001 and 74.5±17.7% vs. 59.0±25.1%, P<0.0001). Subgroups analyses showed that the efficacy of the simulation training was even greater when performed at the beginning of residency (P<0.0001). After the training, the duration to perform a complete TEE was significantly lower in the simulation group than in the traditional group (respectively 8.3±1.4 min vs. 9.4±1.2 min, P<0.0001). Finally, residents' feelings were better in the simulation group than in the traditional group across all components (P<0.0001). Compared to the traditional group, the average additional cost per resident of the simulation program was respectively €1,785, €942 or €662 for 20, 40 and 60 residents. Conclusion Simulation-based teaching on TEE showed a significant improvement in knowledge, skills, and feelings of cardiology residents as well as a reduction in the duration to complete the examination. Funding Acknowledgement Type of funding sources: None