The National Clinical Trials Network (NCTN) Biospecimen Banks

This paper reports the first validated predictive biomarker test that can identify which patients can avoid, and those most likely to get benefit from adding antiandrogens to their radiation therapy for prostate cancer. The test is based on an artificial intelligence image analysis (AIIA) algorithm developed using digital images from 16,277 H&E slides from 5727 patients enrolled on 5 NRG Trials; RTOG-9202, RTOG-9408, RTOG-9413, RTOG-9910, RTOG-0126, and is an expansion of prior work done with this set of patients’

Rhabdomyosarcoma is the most common soft tissue sarcoma of childhood. Despite aggressive therapy, the 5-year survival rate for patients with metastatic or recurrent disease remains poor, and beyond PAX-FOXO1 fusion status, no genomic markers are available for risk stratification. This publication addresses the largest genomic characterization of clinically annotated rhabdomyosarcoma tumors to date and provides prognostic genetic features that refine risk stratification and will be incorporated into prospective trials.

This study reports the discovery of somatic mutations in the chemokine gene CCL22 as the hallmark of a distinct subset of Chronic lymphoproliferative disorder of natural killer cells (CLPD-NK). Somatic CCL22 mutations illustrate a unique mechanism of tumor formation in which gain-of-function chemokine mutations promote tumorigenesis by biased GPCR signaling and dysregulation of microenvironmental crosstalk. Acute NK leukemia samples were provided by the ECOG-ACRIN Cancer Research Group.

In this predictive prognostic study in which a combined correlative analysis of the CALGB (Alliance) 40601 and PAMELA trials was conducted, 305 patients with early-stage ERBB2/HER2-positive breast cancer, 6 B-cell–related signatures were more strongly associated with pathologic complete response than were tumor-infiltrating lymphocytes. In a multivariable Cox model performed in the CALGB 40601 trial, the immunoglobulin G signature, but not tumor-infiltrating lymphocytes, was independently associated with event-free survival. These findings suggest that when both tumor-infiltrating lymphocytes and gene expression analysis results are available, the prognostic and predictive value of RNA sequencing–based immune signatures is superior.

The prognostic role of stromal tumor-infiltrating lymphocytes (sTILs) and DNA Damage Immune Response (DDIR) in early-stage Triple-Negative Breast Cancer (TNBC) was confirmed. DDIR signature conferred improved prognosis in two thirds of patients with TNBC treated with adjuvant doxorubicin (A) and cyclophosphamide (C). DDIR signature has the potential to stratify outcome and to identify patients with less projected benefit after AC chemotherapy. In summary, This study identified the DDIR signature and sTILs as predictive of improved disease-free survival and overall survival for TNBC in the context of adjuvant AC chemotherapy.

This publication is the most recent in a body of work that involved a GWAS done on more than 4000 patients from the NCTN/CCTG MA.27 trial - A Randomized Phase III Trial of Exemestane Versus Anastrozole in Postmenopausal Women with Receptor Positive Primary Breast Cancer. This particular study looked at the association of specific SNPs and outcomes and identified SNPs that differentiate the efficacy of anastrozole and exemestane. The results suggest that additional genetic biomarkers may be useful for selecting an AI for a given patient.