Articles in 2011

The ECOG E4201 study adds another piece of information to a growing body of evidence pointing strongly to the importance of local control and the role of radiotherapy in unresectable pancreatic cancer. Based on this evidence, we believe radiotherapy should be used routinely in this setting.boxed-text

Screening for prostate cancer using PSA is a careful balance of benefits and harms. But current US practice involves testing older men who have little to gain and aggressively treating low-risk cancers. Debates about whether to test need to be replaced by debates on how to test better.

Despite the advent of HER2-directed therapies, many patients with HER2-positive early stage breast cancer relapse and die of this disease. Trials to define, refine and optimize the use of the approved HER2-targeted agents are ongoing. New approaches are being developed and a series of large trials in the adjuvant and neoadjuvant settings are planned or in progress. In this Review, Arteaga et al. describe the current treatment for HER2-positive breast cancer and provide an update on ongoing clinical trials and translational research.

This Review discusses recent evidence that indicates that different genetic alterations might be related to distinct sensitivity to targeted therapies. It examines prototypical examples and asks what is the role of cancer mutations as predictors of sensitivity and resistance to targeted therapies? Further, what are the implications for the 'personalized' treatment of cancer patients?

The AZURE trial data add to the uncertainty of whether adjuvant bisphophonates are a valuable addition to the armamentarium in the treatment of early stage breast cancer. Although the overall trial results were negative, a prespecified subgroup analysis demonstrated a 25% reduction in the risk of relapse and death in postmenopausal patients.

The size, length and cost of phase III clinical trials are prompting oncology researchers and pharmaceutical companies to look for other options. This Review outlines adaptive clinical trial designs that can address many questions at once. A wholly new paradigm for drug development exemplifying personalized medicine is evinced by an adaptive trial called I-SPY2, in which drugs from many companies are evaluated in the same study and are matched with their biomarker signatures.

Radioimmunotherapy is being used successfully for the treatment of patients with hematological malignancies, however similar efficacy is lacking in patients with solid tumors. Pouget and colleagues explain basic concepts of radiobiology, review the results of clinical radioimmunotherapy trials, and highlight potential strategies to improve the efficacy of radioimmunotherapy in patients with solid tumors.

In a trial in patients with metastatic breast cancer, the prognostic value of the number of circulating tumor cells (CTCs) at baseline was independent of tumor subtype, except in patients with HER2-positive disease treated with anti-HER2 targeted therapy. These data support the use of CTC detection as a tool contributing to personalized medicine.

The Cancer Act that was signed by President Nixon in December 1971 had a mandate “to support research and the application of the results of research, to reduce the incidence, morbidity and mortality from cancer.” It has succeeded in many of these aims, as this personal account testifies.

Carcinomas of an unknown primary origin (CUP) are histologically confirmed metastases for which a primary tumor could not be found despite an extensive diagnostic workup of the patient. The authors of this Review discuss the clinical evaluation of patients with CUP, describe how to identify specific CUP subsets, and outline treatment strategies and outcomes of patients with CUP.