Viewpoint

In this Viewpoint the potential implications of improved understanding of the metastatic cascade in cancer patients are discussed. The detection of disseminated tumor cells before the onset of overt metastasis could improve stratification of patients who are in need of early systemic anti-cancer therapy; monitor the efficacy of such therapy; help to identify therapeutic targets; and assist in selection of cancer patients who are candidates for targeted therapies.

Therapy that effectively shrinks tumor bulk is often unable to completely eliminate disease. One theory is that chemotherapeutic agents target rapidly growing cells, but can leave a pool of slowly proliferating, quiescent cells (stem cells) unharmed. These cells can then divide and reestablish the tumor once therapy ceases. This Viewpoint presents evidence that gastric cancer stem cells could originate from bone marrow.

Older patients are less likely to receive standard treatments for cancer than similar younger patients. Arti Hurria proposes a specific oncology geriatric assessment, including functional status, comorbid medical conditions, nutritional status, cognitive function, psychological state and social support, and medication review, to pinpoint an individual's functional age and facilitate appropriate care.

Cancer incidence and mortality are expected to rise substantially in low-income countries. Franco Cavalli outlines how we should react to this threat, and gives guidance on preventive measures that can be tailored to different resource settings.

The dilemma for those managing patients with cancer and neutropenia is whether the potential benefit of fluoroquinolones outweigh their disadvantages—drug resistance, toxicity and cost. The authors of this Viewpoint re-examine the question of who (if anyone) should receive fluoroquinolone prophylaxis.

Evidence gained in randomized controlled trials (RCTs) is considered superior to that gained from associated epidemiological studies, but both types of study can be prone to error. Issues such as reproducibility, recall bias and duration are important factors that contribute to these errors, as discussed in this Viewpoint.

Developing chemotherapeutic regimens that can be given at the optimal dose and schedule continues to be one of the greatest challenges in clinical oncology. Simon and Norton discuss how they used guiding principles to derive the Norton–Simon hypothesis, and describe how this has improved clinical trial design and helped to achieve the goal of more effective and less toxic chemotherapeutic regimens.

Early treatment of pancreatic cancer increases the likelihood of survival, but detection of the disease is difficult in the early stages. The authors of this Viewpoint recommend screening populations at increased risk of developing pancreatic cancer because of family history, to identify early disease in a higher proportion of patients.

The effectiveness of renal cryoablation is difficult to determine in the absence of specific clinical research protocols, and the role of this technique in the treatment of small renal masses cannot yet be defined as a paradigm shift.

No single indicator provides unambiguous information regarding the population burden and dynamics of breast cancer. Milena Sant and co-authors discuss the trends in incidence, survival and mortality for patients with breast cancer in Western Europe and suggest a strategy for analysis of these data.

Although the epidermal growth factor receptor tyrosine kinase inhibitors gefitinib and erlotinib can produce dramatic and durable tumor responses, not all patients with non-small-cell lung cancer (NSCLC) benefit from these drugs. This Viewpoint discusses the molecular correlates of response for these agents in patients with NSCLC.

When is chemotherapy too well tolerated? This Viewpoint discusses the possibilities that some patients receive inadequate doses of chemotherapy using the conventional dose calculation method based on body surface area and that a correlation between hematological toxicity and treatment efficacy could be used to titrate therapy.

Glioblastoma multiforme (GMB) is a devastating neoplasm that nearly always culminates in death within 1–2 years of diagnosis. Despite decades of intensive clinical and laboratory research, progress has been slow, partly because of limited drug delivery and tumor heterogeneity. David Reardon describes an innovative chemoradiation approach that has improved overall survival for newly diagnosed GBM patients, and details a number of promising therapeutic strategies under evaluation.

The Investigational New Drug (IND) process was established to ensure that the FDA is informed of any new treatment before use in humans. The process is now used for approval rather than notification. The time from conception to approval for a new drug is estimated at over 15 years, of which two-thirds is devoted to pre-IND testing. In the meantime the patient is denied access to the investigational treatment. A centralized IND procedure, when the public are already protected by processes within academic centers of excellence, is redundant and costs lives.

Women withBRCA1/2mutations have a higher risk of breast and ovarian cancer than the general population. The authors outline current evidence for strategies to reduce the risks of cancer development in these women, and discuss future research directions.

In low-resource regions of the world, women with breast cancer often do not present themselves for treatment until the disease has reached an advanced stage. This article offers some cost-effective and practical recommendations for early detection, diagnosis and treatment of breast cancer in low-resource countries.

Development of therapies directed to specific molecular abnormalities within cancer cells, as exemplified by human epidermal growth factor receptor 2 (HER2), can be a very rewarding strategy in cancer treatment. The integration of genomic and proteomic approaches into the search for therapeutic targets will be more fruitful than either approach alone and allow further individualization of breast cancer therapy.

Substantial progress has been made using aromatase inhibitors in early-stage breast cancer. This article highlights results from recent and ongoing trials of aromatase inhibitors as adjuvant therapy and discusses options for integration of these agents with tamoxifen in various subsets of patients and clinical scenarios.

The evidence for prostate cancer screening using prostate-specific antigen with reference to UK criteria is presented. Such screening might result in considerable over-diagnosis and over-treatment of clinically insignificant prostate cancer. Morbidity associated with treatment of suspected prostate cancer is substantial, so the likelihood of harm may outweigh the prospect of benefit.

This Viewpoint assesses whether prostate cancer screening within the US is justifiable outside clinical trials. Prostate-specific antigen (PSA) values may fluctuate for physiologic reasons and the natural history of the disease varies between individuals. PSA testing increasingly identifies too many cases of indolent disease that would never have threatened patients' lives.