Milosevic et al. Page 2108

Hypoxia is important in many human cancers and influences clinical behavior, development of metastases, and patient survival. This prospective study by Milosevic and colleagues in 247 men with intermediate-risk prostate cancer demonstrates, for the first time, that tumor hypoxia measured prior to treatment is associated with early biochemical recurrence after escalated-dose radiotherapy. This pattern of recurrence is compatible with the presence of hypoxia-driven occult metastases. The results of this study provide new insight about the biologic behavior of prostate cancer after radiotherapy and have important implications for combining radiotherapy with hypoxia-targeted therapeutics or other systemic anticancer treatments.

Visco et al. Page 1870

Immune thrombocytopenia (ITP) is one of the most frequently observed autoimmune complications in patients with chronic lymphocytic leukemia (CLL). Visco and colleagues provide insights into the pathobiology of this event by showing a significant association between ITP occurrence and immunoglobulin heavy-chain variable (IGHV) unmutated gene status, unfavorable cytogenetic lesions, and stereotyped conformation of the B-cell receptor (BCR). In particular, they show that stereotyped IGHV subsets #1 and #7 were significantly the most represented among patients developing ITP. Moreover, they show a prognostic implication for stereotyped BCR subset #7, which was significantly associated with shorter time to ITP development independently of IGHV mutational status. These findings strongly support a role for specific BCR triggering in the pathogenesis of this immune complication in CLL.

Kilday et al. Page 2001

A distinct need exists for novel risk stratification markers to improve outcome in childhood ependymoma. Using interphase FISH, Kilday and colleagues evaluated a prognostic role for 1q25 copy number gain across 3 pediatric European clinical trial cohorts defined according to patient age and adjuvant therapy administered. Gain of 1q25 was shown to be an independent marker of tumor progression for all patients, particularly for younger children treated with primary postoperative chemotherapy. Moreover, incorporating tumor 1q25 status with the degree of surgical resection enabled a novel patient risk-group classification system that was reproducible across all trial groups, thereby advocating the prospective evaluation of 1q25 gain in future international trials of pediatric ependymoma.

Ma et al. Page 2048

Ma and colleagues present their findings from an evaluation of the dual inhibitor of polo-like kinase 1 and phosphoinositide 3-kinase, ON-01910.Na (rigosertib), in combination with gemcitabine in advanced cancer patients with a focus on pancreatic adenocarcinoma. This phase I trial represents the translation of preclinical work that identified rigosertib as a rational agent to modulate the vulnerability of pancreatic cancer to gemcitabine. This clinical study assessed the combination of rigosertib and gemcitabine, its pharmacology, and its preliminary efficacy in patients with pancreatic cancer, finding acceptable tolerability and hints of activity. This study serves as an example of rapid translation of solid preclinical findings to the clinic.