Genomics and Immunomics in the Treatment of Urothelial Carcinoma

Urothelial carcinoma is a complex cancer with genomic immunomic drivers that have prognostic and predictive treatment implications. Identifying potential targetable alterations via next-generation sequencing and RNA sequencing may allow for elucidation of such targets and exploitation with targeted therapeutics. The role of immunotherapy in treating urothelial carcinoma has shown benefit, but it is unclear in which patients immunotherapeutics have the highest yield. Continuing efforts into better identifying which patients may benefit most from targeted therapies, immunotherapies, and combination therapies may ultimately lead to improved outcomes for patients with this disease

A phase 1 trial of SGNâ CD70A in patients with CD70â positive, metastatic renal cell carcinoma

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/148406/1/cncr31912.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/148406/2/cncr31912_am.pd

New coil concept for endoluminal MR imaging: Initial results in staging of gastric carcinoma in correlation with Histopathology

Our aim was to conduct a prospective study to evaluate staging accuracy of a new coil concept for endoluminal magnetic resonance imaging (MRI) on ex vivo gastric carcinomas. Twenty-eight consecutive patients referred to surgery with a clinically proven primary gastric malignancy were included. Surgical specimens were examined with a foldable and self-expanding loop coil (8-cm diameter) at 1.5 Tesla immediately after total gastrectomy. T1- and T2-weighted and opposed-phase sequences (axial, frontal sections; 3- to 4-mm slice thickness) were acquired. Investigators blinded to any patient information analyzed signal intensity of normal gastric wall, gastric tumor, and lymph nodes. Findings were compared with histopathological staging. On surgical specimens, 2–5 gastric wall layers could be visualized. All gastric tumors (26 carcinomas, two lymphomas) were identified on endoluminal MR data (100%). Overall accuracy for T staging was 75% (18/24); sensitivity to detect serosal involvement was 80% and specificity 89%. N staging correlated in 58% (14/24) with histopathology (N+ versus N−). The endoluminal coil concept is feasible and applicable for an ex vivo setting. Endoluminal MR data provided sufficient detail for gastric wall layer differentiation, and therefore, identification of T stages in gastric carcinoma is possible. Further investigations in in vivo settings should explore the potential of our coil concept for endoluminal MR imaging

Concomitant Radioembolization and Immune Checkpoint Inhibition in Metastatic Renal Cell Carcinoma

This case represents the challenge and creativity necessary when treating patients with metastatic renal cell carcinoma who have been exposed to multiple lines of therapy. At present, treatment with immune checkpoint inhibition has stabilized and improved the metastatic disease of this patient with the exception of hepatic lesions. This isolated progression within the liver led the employment of radioembolization, which successfully treated those metastases. This is the first documented case of metastatic renal cell carcinoma controlled with concurrent use of immune checkpoint inhibition and radioembolization for both extrahepatic and hepatic metastases, respectively. This case can be construed as a potential example of the abscopal effect and may provide the basis for understanding this type of response in select patients

Genomics and Immunomics in the Treatment of Urothelial Carcinoma

Urothelial carcinoma is a complex cancer with genomic immunomic drivers that have prognostic and predictive treatment implications. Identifying potential targetable alterations via next-generation sequencing and RNA sequencing may allow for elucidation of such targets and exploitation with targeted therapeutics. The role of immunotherapy in treating urothelial carcinoma has shown benefit, but it is unclear in which patients immunotherapeutics have the highest yield. Continuing efforts into better identifying which patients may benefit most from targeted therapies, immunotherapies, and combination therapies may ultimately lead to improved outcomes for patients with this disease

Multi‐omic analysis in carcinoma of unknown primary (CUP): therapeutic impact of knowing the unknown

Carcinoma of unknown primary (CUP) is a difficult‐to‐manage malignancy. Multi‐omic profiles and treatment outcome vs. degree of precision matching were assessed. Tumours underwent next‐generation sequencing (NGS) [tissue and/or blood‐derived cell‐free DNA (cfDNA)]. Selected patients had transcriptome‐based immune profiling and/or programmed cell death 1 ligand 1 (PD‐L1) immunohistochemistry analysis. Patients could be reviewed by a Molecular Tumor Board, but physicians chose the therapy. Of 6497 patients in the precision database, 97 had CUP. The median number of pathogenic tissue genomic alterations was 4 (range, 0–25), and for cfDNA, was 2 (range, 0–9). Each patient had a distinct molecular landscape. Food and Drug Administration (FDA)‐approved biomarkers included the following: PD‐L1+ ≥ 1%, 30.9% of CUPs tested; microsatellite instability, 3.6%; tumour mutational burden ≥ 10 mutations·Mb−1, 23%; and neurotrophic receptor tyrosine kinase (NTRK) fusions, 0%. RNA‐based immunograms showed theoretically druggable targets: lymphocyte activation gene 3 protein (LAG‐3), macrophage colony‐stimulating factor 1 receptor (CSF1R), adenosine receptor A2 (ADORA2) and indoleamine 2,3‐dioxygenase 1 (IDO1). Overall, 56% of patients had ≥ 1 actionable biomarker (OncoKB database). To quantify the degree of matching (tumours to drugs), a Matching Score (MS; roughly equivalent to number of alterations targeted/total number of deleterious alterations) was calculated post hoc. Comparing evaluable treated patients [MS high, > 50% (N = 15) vs. low ≤ 50% (N = 47)], median progression‐free survival was 10.4 vs. 2.8 months (95% CI 0.11–0.64; HR 0.27; P = 0.002); survival, 15.8 vs. 6.9 months (95% CI 0.17–1.16; HR 0.45; P = 0.09); and clinical benefit rate (stable disease ≥ 6 months/partial/complete response), 71% vs. 24% (P = 0.003). Higher MS was the only factor that predicted improvement in outcome variables after multivariate analysis. In conclusion, CUPs are molecularly complex. Treatments with high degrees of matching to molecular alterations (generally achieved by individualized combinations) correlated with improved outcomes