Computer-Aided Intra-Operatory Positioning of an MRgHIFU Applicator Dedicated to Abdominal Thermal Therapy Using Particle Swarm Optimization.

PURPOSE: Transducer positioning for liver ablation by magnetic resonance-guided high-intensity focused ultrasound (MRgHIFU) is challenging due to the presence of air-filled organs or bones on the beam path. This paper presents a software tool developed to optimize the positioning of a HIFU transducer dedicated to abdominal thermal therapy, to maximize the treatment's efficiency while minimizing the near-field risk. METHODS: A software tool was developed to determine the theoretical optimal position (TOP) of the transducer based on the minimization of a cost function using the particle swarm optimization (PSO). After an initialization phase and a manual segmentation of the abdomen of 5 pigs, the program randomly generates particles with 2 degrees of freedom and iteratively minimizes the cost function of the particles considering 3 parameters weighted according to their criticality. New particles are generated around the best position obtained at the previous step and the process is repeated until the optimal position of the transducer is reached. MR imaging data from in vivo HIFU ablation in pig livers was used for ground truth comparison between the TOP and the experimental position (EP). RESULTS: As compared to the manual EP, the rotation difference with the TOP was on average -3.1 ± 7.1° and the distance difference was on average -7.1 ± 5.4 mm. The computational time to suggest the TOP was 20s. The software tool is modulable and demonstrated consistency and robustness when repeating the calculation and changing the initial position of the transducer.

Olaparib not cost-effective as maintenance therapy for platinum-sensitive, BRCA1/2 germline-mutated metastatic pancreatic cancer.

OBJECTIVE: To assess the cost-effectiveness and budget impact of olaparib as a maintenance therapy in platinum-responsive, metastatic pancreatic cancer patients harboring a germline BRCA1/2 mutation, using the Swiss context as a model. METHODS: Based on data from the POLO trial, published literature and local cost data, we developed a partitioned survival model of olaparib maintenance including full costs for BRCA1/2 germline testing compared to FOLFIRI maintenance chemotherapy and watch-and-wait. We calculated the incremental cost-effectiveness ratio (ICER) for the base case and several scenario analyses and estimated 5-year budget impact. RESULTS: Comparing olaparib with watch-and wait and maintenance chemotherapy resulted in incremental cost-effectiveness ratios of CHF 2,711,716 and CHF 2,217,083 per QALY gained, respectively. The 5-year costs for the olaparib strategy in Switzerland would be CHF 22.4 million, of which CHF 11.4 million would be accounted for by germline BRCA1/2 screening of the potentially eligible population. This would amount to a budget impact of CHF 15.4 million (USD 16.9 million) versus watch-and-wait. CONCLUSIONS: Olaparib is not a cost-effective maintenance treatment option. Companion diagnostics are an equally important cost driver as the drug itself.

Immunotherapy and Gastrointestinal Toxicities.

Gastrointestinal toxicities secondary to immune checkpoint inhibitors are very frequent. Because in some instances this can be severe or fatal, it is essential to be able to identify immune-related adverse events rapidly. Prompt initiation of systemic immunosuppression can improve outcomes. A biopsy is often necessary to confirm the diagnosis of immune-related adverse events. Moderate or severe irAEs need an interruption of ICI. After the resolution of the toxicities, the rechallenge of immune checkpoint inhibitors must be discussed case by case.