Lucas Padilha

The gut microbiota influences the clinical responses of cancer patients to immunecheckpoint inhibitors (ICIs). However, there is no consensus definition of detrimental dysbiosis. Based on metagenomics (MG) sequencing of 245 non-small cell lung cancer (NSCLC) patient feces, we constructed species-level co-abundance networks that were clustered into species-interacting groups (SIGs) correlating with overall survival. Thirty-seven and forty-five MG species (MGSs) were associated with resistance (SIG1) and response (SIG2) to ICIs, respectively. When combined with the quantification of Akkermansia species, this procedure allowed a person-based calculation of a topological score (TOPOSCORE) that was validated in an additional 254 NSCLC patients and in 216 genitourinary cancer patients. Finally, this TOPOSCORE was translated into a 21-bacterial probe set-based qPCR scoring that was validated in a prospective cohort of NSCLC patients as well as in colorectal and melanoma patients. This approach could represent a dynamic diagnosis tool for intestinal dysbiosis to guide personalized microbiota-centered interventions.

Background: It is suggested that survivors of different types of cancer may have an increased risk of stroke. Our study aims to evaluate cancer patients and non-cancer controls by analyzing stroke events in each group. Previous studies concluded that certain types of cancer increased stroke risk, however, their results had significant heterogeneity and statistical concerns. Methods: Medline, Embase, and Cochrane databases were systematically searched until February 18th, 2024, assessing stroke in cancer survivor patients compared to the global population. Data were examined using the Mantel-Haenszel method and 95% CIs. Heterogeneity was assessed using I 2 statistics. Review Manager 5.4 was used for statistical analysis. Results: A total of 18 studies were included, and stroke was reported in both cancer and non-cancer groups. Breast cancer (HR 1.09; 95% CI 1.02-1.17; p=0.01; I 2 = 0%), Central Nervous System cancers (HR 2.47; 95% CI 1.01-6.01; p=0.05; I 2 = 78%), cervical cancers (HR 1.58; 95% CI 1.19-2.09; p=0.001; I 2 = 0%), head and neck cancers (HR 1.34; 95% CI 1.07-1.68; p=0.01; I 2 = 59%), lung cancers (HR 1.60; 95% CI 1.40-1.83; p<0.00001; I 2 =67%), multiple myeloma (HR 1.58; 95% CI 1.32 -1.89; p<0.00001; I 2 = 49%), nasopharyngeal cancers (HR 1.72; 95% CI 1.28-2.30; p=0.0003; I 2 = 85%), oesophageal cancers (HR 1.33; 95% CI 1.07-1.65; p=0.009; I 2 = 0%), ovarian cancers (HR 1.33; 95% CI 1.07-1.65; p=0.01; I 2 = 38%), pancreatic cancers (HR 2,70; 95% CI 2.34-3.11; p<0.00001; I 2 = 0%) and rectum cancers (HR 1.29; 95% CI 1.01-1.63; p=0.04; I 2 = 0%) showed statistically significant differences between groups in favor of non-cancer controls. Conclusions: In this meta-analysis, the stroke risk was increased in all cancers that reached statistical significance. Furthermore, our study brings relevant data to the body of literature concerning this long-term clinical uncertainty.