Evaluation of cell-free DNA approaches for multi-cancer early detection.

In the Circulating Cell-free Genome Atlas (NCT02889978) substudy 1, we evaluate several approaches for a circulating cell-free DNA (cfDNA)-based multi-cancer early detection (MCED) test by defining clinical limit of detection (LOD) based on circulating tumor allele fraction (cTAF), enabling performance comparisons. Among 10 machine-learning classifiers trained on the same samples and independently validated, when evaluated at 98% specificity, those using whole-genome (WG) methylation, single nucleotide variants with paired white blood cell background removal, and combined scores from classifiers evaluated in this study show the highest cancer signal detection sensitivities. Compared with clinical stage and tumor type, cTAF is a more significant predictor of classifier performance and may more closely reflect tumor biology.

Sperm-derived SPANX-B is a clinically relevant tumor antigen that is expressed in human tumors and readily recognized by human CD4+ and CD8+ T cells.

Purpose: The sperm-derived SPANX family proteins can be found expressed in human tumors. Here, we aimed to perform a comprehensive study to evaluate immunotherapeutic relevance of one of its members, SPANX-B. We wanted to test its expression pattern in human tumors and to evaluate CD4(+) and CD8(+) T-cell responses in healthy humans after in vitro immunizations.

Intraperitoneal chemotherapy: standard of care for patients with minimal residual stage III ovarian cancer?

Epithelial ovarian cancer is the leading cause of death from gynecological cancer in most of the Western world, and long-term survival remains poor despite good initial response to systemic therapy after debulking surgery. Even after complete pathological response, the risk of recurrence in the first few years is substantial. The peritoneum is the predominant site of failure and the disease remains confined to the peritoneal cavity for much of its course.

Phase II open-label study of oral piritrexim in patients with advanced carcinoma of the urothelium who have experienced failure with standard chemotherapy.

Background: Piritrexim is reported to have a response rate of 38% in patients with chemotherapy-naive disease and 23% for second-line therapy after chemotherapy failure. We report the results of a multiinstitutional, open-label, 2-stage, phase II study that further evaluates oral piritrexim in patients with urothelial carcinoma and who proved nonresponsive to standard chemotherapy.

Patients And Methods: Eligible patients included those with bi-dimensionally measurable disease and an Eastern Cooperative Oncology Group performance status of 0-2, transitional cell carcinoma or adenocarcinoma of the urothelium, and nonresponse to > or = 1 previous standard chemotherapy regimen.

Recent developments in germ cell tumors of the testes.

Purpose Of Review: An overview on several important developments in testicular germ cell tumors in the past year is provided.

Recent Findings: Despite being highly treatable even in advanced stages, recent studies demonstrate that testicular germ cell tumor mortalities can vary significantly in different regions of the world, suggesting limited access to appropriate treatments in certain geographic regions. Several clinically relevant studies on the role of retroperitoneal lymph node dissection in early and advanced stages of disease, and chemotherapy, particularly high-dose chemotherapy in the first-line and salvage settings, were reported.

Recurrent ovarian cancer.

Ovarian cancer is the most common cause of death from gynecologic malignancies in the United States. Although ovarian cancer is very responsive to multiple chemotherapeutic agents, with objective response rates of up to 80% with the standard platinum and taxane doublets, 75% of patients relapse within 2 years of primary therapy and become candidates for treatment of recurrent disease. Recurrent ovarian cancer is increasingly approached as a chronic disease that requires sequential therapy with available agents.