Deep space orbit determination and guidance of the LICIACube microsatellite mission

Recently, the JPL's MarCO mission demonstrated that these probes are also mature enough to be employed in the deep space, even though with the limitations related to the employed commercial components. Currently, other deep space CubeSats are planned either as stand-alone missions or as companions of a traditional large probe. Therefore, developing a dedicated navigation suite is crucial to reaching the mission's goals, considering the limitations of the onboard components compared to typical deep space missions. In this framework, the LICIACube mission represents an ideal candidate test-bench, as it performs a flyby of the Didymos asteroid system subject to a strong position, epochs, and pointing requirements. This mission will also allow us to infer the capabilities of such microsatellites and highlight their limitations compared with the benefits of a lighter design and tailoring efforts. In this work, the OD and guidance methods and tools adopted for classical deep space missions have been tailored for the CubeSat applications and validated through extensive analyses. In addition, navigation procedures and interfaces have been designed in view of the operations foreseen in late 2022. The pre-launch covariance analysis has been performed to assess the mission's feasibility for the nominal trajectory and its associated uncertainties, based on conservative assumptions on the main parameters. Extensive sensitivity analyses have been carried out to understand the main mission parameters affecting the performance and to demonstrate the robustness of the designed trajectory and operation schedule in fulfilling the mission requirements. The developed system was also stressed by tuning the models to access different reconstruction methods for the maneuvers. The analysis demonstrated the feasibility of the LICIACube mission navigation in compliance with the mission requirements, compatible with the limited resources available, both in space and on the ground.

The RAS-Lung project: implementing blood and tissue genotyping in KRAS-Positive non-small cell lung cancer treatment

Background: The frontline management of non-oncogene addicted non-small cell lung cancer (NSCLC) involves immunotherapy (ICI) alone or combined with chemotherapy (CT-ICI). As therapeutic options expand, refining NSCLC genotyping gains paramount importance. The dynamic landscape of KRAS-positive NSCLC presents a spectrum of treatment options, including ICI, targeted therapy, and combination strategies currently under investigation. Methods: The two-year RASLUNG project, featuring both retrospective and prospective cohorts, aimed to analyze the predictive and prognostic impact of KRAS mutations on tumor tissue and circulating DNA (ctDNA). Secondary objectives included assessing the roles of co-mutations and longitudinal changes in KRAS mutant copies concerning treatment response and survival outcomes. An external validation study confirmed the prognostic or predictive significance of co-mutations. Results: In the prospective cohort (n=24), patients with liver metastases exhibited significantly elevated ctDNA levels(p=0.01), while those with >3 metastatic sites showed increased Allele Frequency (AF) (P=0.002). Median overall survival (OS) was 7.5 months, progression-free survival (PFS) was 4.0 months, and the objective response rate (ORR) was 33.3%. Higher AF correlated with an increased risk of death (HR 1.04, p = 0.03), though not progression. Notably, a reduction in plasma DNA levels was significantly associated with objective response(p=0.01). In the retrospective cohort, KRAS and STK11 mutations co-occurred in 14/21 patients (p=0.053). STK11 mutations were independently detrimental to OS (HR 1.97, p=0.025) after adjusting for various factors. KRAS tissue AF did not correlate with OS or PFS. Within the validation dataset, STK11 mutations were significantly associated with an increased risk of death in univariate (HR 2.01, p<0.001) and multivariate models (HR 1.66, p=0.001) after adjustments. Conclusion: The RAS-Lung Project, employing innovative genotyping techniques, underscores the significance of comprehensive NSCLC genotyping. Tailored next-generation sequencing (NGS) and ctDNA monitoring may offer potential benefits in navigating the evolving landscape of KRAS-positive NSCLC treatment.