Matthew S. Ning

Cervical and Tumor-Associated Microbiomes in Botswana Women With and Without HIV With Carcinoma of the Cervix Before and After Definitive Chemoradiation

PURPOSE Cervical cancer remains a significant public health concern globally and particularly in sub-Saharan Africa, where high rates of HIV infection exacerbate cervical cancer incidence. Understanding the cervical microbiome and its role in cancer progression is essential, especially in regions where both cervical cancer incidence and HIV prevalence are high. This study aimed to characterize the cervical microbiome in women living with HIV (WLWH) and HIV-negative women with squamous cell carcinoma of the cervix in Botswana, compare the microbiome between before and after chemoradiation therapy (CRT) in WLWH, and assess the prognostic value of specific microbial taxa for overall survival (OS) in WLWH. PATIENTS AND METHODS Cervical samples were collected from women with cervical cancer presenting to one hospital in 2018-2019. Patients' clinical data, including HIV status, were recorded. Microbial composition was analyzed using 16S rRNA gene sequencing. Microbiome diversity and composition were evaluated using alpha and beta diversity metrics. Differential microbial abundance was analyzed using linear discriminant analysis effect size. The association between microbial taxa and OS was explored using Cox proportional hazards regression. RESULTS WLWH (n = 42) had a significantly lower Pielou evenness index than HIV-negative women (n = 11; 0.6 v 0.7, P = .02), suggesting a more imbalanced microbiome in WLWH. WLWH had higher levels of Parvimonas and members of the Corynebacteriaceae and Micrococcaceae families, suggesting a shift toward a more pathogenic microbiome. In WLWH, CRT did not significantly alter overall microbial diversity. However, Lactobacillus and Sutterella were enriched before treatment, reflecting a less pathogenic microbiome, whereas Ruminococcus and Phascolarctobacterium and the families Caulobacterales and Flavobacteriia were enriched after treatment, reflecting microbial adaptations to the altered immune and treatment environment. Notably, higher levels of Flavobacteriia after CRT were independently associated with worse OS in WLWH. CONCLUSION Microbiome profiles differ between WLWH and HIV-negative women with cervical cancer in Botswana. The microbiome might have prognostic significance. Future research is needed to better understand the significance of the microbiota in cervical cancer progression and treatment outcomes and the potential role of microbiome-targeted interventions.

Iterative intraoperative 3T MRI (iMRI)-guided brachytherapy: A prospective study on enhancing implantation precision and dosimetric gains in advanced gynecologic cancers

To report on primary outcomes and dosimetric results of a prospective clinical trial and protocol for use of iterative intraoperative magnetic resonance imaging (iMRI) in gynecologic brachytherapy. Patients with locally advanced cervical or vaginal cancer (FIGO stages IB2 - IVA, and stage II-IVA, respectively) undergoing pulsed dose rate (PDR) brachytherapy were enrolled in a prospective clinical trial (NCT03634267) using iterative 3T iMRI during brachytherapy implant placement. Applicator and optional interstitial needles were placed under iMRI guidance in a 3T clinical MRI scanner. Imaging, dosimetry and clinical outcomes (local control (LC), recurrence-free survival (RFS), overall survival (OS)), and acute and long-term toxicity were evaluated prospectively and confirmed by chart review. To explore dosimetric gains, an EQD2 estimate comparing iMRI-guidance versus standard of care guidance, as well as a 3-patient analysis of dose changes with iMRI-guided optimization was included. Fourteen patients underwent iMRI-guided brachytherapy. Seventy percent (70%) of patients presented with FIGO stage III disease or higher. Median follow-up was 44 months. . Patients had 2-year median LC, RFS, and OS rates of 83.3%, 76%, and 84.6%, respectively. Acute toxicities were minimal with one (1) case of grade 3 nausea. No grade 3 or higher long-term toxicities were observed. Median operating room (OR) time was 283 minutes (range 174-380 mins). On exploratory analysis, implant placement performed with iMRI guidance demonstrated higher HR-CTV D90 doses (mean difference of +784.7 cGy, p = NS) were achieved compared to US and CT guided implantation in the same patients. iMRI-guidance for gynecologic brachytherapy is safe, associated with minimal high-grade toxicity and excellent clinical outcomes. Future studies to optimize resource use, image acquisition efficiency, and identifying predictive imaging features are warranted.