Reviews & Analysis

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.

Post-therapy prostate-specific antigen (PSA) changes have been associated with improved survival in castrate metastatic patients, but currently no drug has been approved strictly on the basis of a post-treatment decline in PSA, as it is unproven that such PSA changes are surrogates for true clinical benefits. Fleming and coauthors address the critical question of whether PSA post-therapy decline reflects true clinical benefit, and if it should be used as an intermediate endpoint for accelerated approval. The authors emphasize the importance of recognizing that there are a range of clinical benefits to patients that can favorably improve the quality and possibly the duration of survival independent of PSA.

Experimental data indicate that lymphodepletion prior to adoptive transfer of tumor specific T-lymphocytes plays a key role in enhancing treatment efficacy by eliminating regulatory T-cells and competing elements of the immune system. Newly emerging animal data suggest that more profound lymphoablative conditioning with autologous hematopoetic stem-cell rescue might further enhance treatment results. The authors review the recent advances in adoptive immunotherapy of solid tumors and discuss the rationale for lymphodepleting conditioning, and also address the safety issues of translating experimental animal results of total lymphoid ablation into clinical practice.

Vascular disrupting agents (VDAs) are designed to disrupt the already established abnormal vasculature, and induce rapid shutdown of tumor blood supply causing subsequent tumor death from hypoxia and nutrient deprivation. The authors discuss the strategies to improve drug delivery, and suggest that further clinical trials need to evaluate novel treatment strategies that combine VDAs with radiotherapy, cytotoxic drugs, anti-angiogenic agents, and other novel targeted therapies. Close attention to the cardiovascular side effect profile of these agents is also imperative during their clinical development.

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.

Surgery and chemotherapy form the cornerstone in the treatment of ovarian cancer. The standard of care for primary ovarian cancer is platinum and taxane-based chemotherapy. Despite the favorable response characteristics, however, most women with advanced-stage ovarian cancer will relapse. Herzog and Pothuri discuss the treatment options available and highlight the issues surrounding how these patients should be managed with surgical, chemotherapy, biological targeted agents and radiation therapy.

Adjuvant chemotherapy improves survival for patients with early-stage disease but this benefit is not equal for all patients. Molecular characteristics of the cancer affect sensitivity to chemotherapy. In general, estrogen receptor (ER)-negative disease is more sensitive to chemotherapy than ER-positive tumors. Before any new molecular classification (or predictive test) is adopted for routine clinical use, however, several criteria need to be met. This review describes the current limitations and future promises of gene-expression-based molecular classification of breast cancer and how it might impact selection of adjuvant therapy for individual patients.

It is unclear whether stressful life events, work-related stress, or perceived global stress are differentially associated with breast cancer incidence and breast cancer relapse in prospective studies. In this review systematic and explicit methods were used to identify, select, and critically appraise relevant studies. Despite the heterogeneity in the results obtained, the authors conclude that stress does not seem to increase the risk of breast cancer incidence but emphasize that larger studies on stress and breast cancer relapse are required to determine if stress affects the progression of breast cancer.

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.

The development of the 70-gene prognosis signature for breast cancer was evaluated in the MINDACT (Microarray In Node negative Disease may Avoid ChemoTherapy) trial to assess the clinical relevance of the 70-gene prognosis signature, and how this compares with traditional prognostic factors for assigning adjuvant chemotherapy for patients with node-negative breast cancer. This review outlines the background work and rationale behind the final design of the MINDACT trial and how these considerations can help to optimize future trials and aim to improve individualization of cancer therapy.

Owing to cardiovascular and thromboembolic toxicities, oral estrogens were abandoned as treatments for prostate carcinoma; however, it is now recognized much of this toxicity can be avoided by parenteral (intramuscular or transdermal) estrogen administration. Ockrim and coauthors highlight the cost and protective andropause advantages of estrogen therapy, advocating a re-evaluation of this promising, but forgotten therapy.

The established role of theRETproto-oncogene in the development of medullary thyroid carcinoma makes this gene an attractive target for selective cancer therapy. The current evidence of RET involvement in the etiology of medullary thyroid carcinoma, and the therapeutic targeting of this process in preclinical and clinical studies are discussed, and the authors propose why targeting the RET proto-oncogene with small-molecule drugs is very likely to be successful in clinical applications.

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.

The importance of positive N2 lymph node staging for prognosis and treatment decisions is now recognized for patients with Pancoast tumors. The authors of this review assert that a multi-disciplinary management strategy is needed for these patients, and that survival advantages have been observed using combined and multimodality regimens. The role of surgery in the context of viable treatment options and the use of imaging for assessing treatment response is critically discussed.

Sedation is used in multiple settings in palliative care, such as transient controlled sedation, respite sedation, and sedation for refractory psychological or existential suffering; however, it is a controversial technique that can diminish the capacity of the patient to interact, function, and, in some cases, to live. Cherny provides a comprehensive account of the risks associated with different sedation approaches and also highlights the controversies and ethical considerations for palliative care medicine.

Advances in the fields of genetics and gene-expression profiling and the advent of microarray technology have revolutionized the concept of patient tailored treatment. Before microarrays qualify as a useful clinical tool, however, they must demonstrate reliability and reproducibility. Limitations of microarray technology include sample acquisition and methods of biostatistical analysis required to analyze the enormous quantities of data obtained. Abdullah-Sayaniet al.overview the current status of microarray technology in clinical practice and propose how advances in this technology will help eliminate some of these limitations and improve patient management.