Reviews & Analysis

Suboptimal studies had established preoperative chemoradiation as the preferred strategy in the management of localized oesophageal cancer (LEC) and gastro-oesophageal cancer. The recent CROSS trial has now demonstrated considerable benefit from preoperative chemoradiation over surgery alone in patients with LEC. But, are these results only reinforcing advocates of the preoperative chemoradiation strategy?

Most studies for identifying biomarkers for oestrogen receptor-α (ERα)-positive breast cancer have been performed using material from consecutive series of patients treated with tamoxifen. Consequently, the predictive value of any biomarker identified is confounded by its prognostic value. In this Review, the authors discuss how different biomarkers might enable the prediction of broad endocrine or agent-specific resistance.

The identification ofBRCA1 and BRCA2 mutations has affected multiple aspects of breast cancer care, including screening and prevention. The authors discuss therapies that have quickly entered clinical practice and highlight some of the challenges in the development of targeted therapies in BRCA1 and BRCA2mutation carriers, as well as specific issues in the area of diagnostic testing related to these targeted therapies.

The needs and treatment requirements of older patients with cancer are different to their younger counterparts. However, few data are available on which to base important clinical decisions for the treatment of this patient population. This Review article outlines the issues and some of the solutions associated with treating cancer in older patients and uses three case studies to illustrate the practical problems that clinicians face.

This Review describes current strategies and future approaches to improve T cell-based therapies to treat post-transplant lymphoproliferative disease, a serious and often life-threatening complication that is associated with Epstein-Barr virus and can occur after haematopoietic stem-cell or solid organ transplantation.

Treatment of locally advanced non-small-cell lung cancer (NSCLC) in the elderly is challenging, with many available treatment options from radiotherapy alone to sequential chemoradiation. The latest phase III trial comparing radiotherapy alone with concurrent chemoradiation reported a survival improvement for the combination; however, this does not define a new standard treatment.

The use of tumour molecular profiles for therapeutic decision making requires that molecular diagnostics be introduced into routine clinical practice. To this end, the French National Cancer Institute and French Ministry of Health have set up a national network of 28 regional molecular genetics centres. In this Perspectives article, the authors look at the 4-year history of the French initiative and discuss its success in rapidly implementing molecular tests for new tumour biomarkers.

Venous thromboembolism (VTE) is a potentially life-threatening condition that can be associated with significant morbidity and is linked to cancer by numerous pathophysiological mechanisms. Here, the risk factors, mechanisms, prevention, and optimal treatment of VTE in patients with cancer are discussed.

The PALETTE randomized phase III trial has reported a statistically significant benefit for the use of pazopanib compared to placebo in terms of progression-free survival for the treatment of soft-tissue sarcoma. However, no benefit in terms of overall survival was observed, the reasons for which might lie in the study design.

A multidisciplinary colloquium—Developing Strategies for Reducing Cancer Treatment-Related Toxicities and Symptoms—was held to identify the challenges that have prevented progress in reducing cancer-treatment-related symptom burden and to develop strategic steps to meet these challenges. This Perspectives article summarizes the recommendations of the panel, and includes suggestions for improving cancer care in the clinic and developing a policy and advocacy strategy to expand research on toxicity.

Breast cancers in young women are typically aggressive and so young age can correlate with a poorer outcome. In this Review article, Steven Narod discusses the risk factors, risks of recurrence and secondary cancer, treatment, prevention and awareness of very-early onset breast cancer.

Life expectancy of most patients with differentiated thyroid cancer is normal, so adverse treatment effects should be minimized. Lower activities of radioiodine for ablation of thyroid remnants are non-inferior to higher activities and quality of life can be maintained by preparation of radioiodine remnant ablation using recombinant human thyrotropin.

In a randomized phase III trial of induction therapy in adult acute myeloid leukaemia, the addition of cladribine, but not fludarabine, to daunorubicin and cytarabine seemed to improve complete response rates and overall survival. However, serious methodological problems make it difficult to estimate the actual clinical importance of the result.

Hodgkin lymphoma has become one of the most successfully treatable cancers; nevertheless, adverse treatment-related side effects still occur. In this Review, Borchmann et al. discuss the current choices for patients with Hodgkin lymphoma by finding the balance between optimal disease control and the risk of long-term sequelae.

Recent evolution of prostate cancer treatment reflects technological arms races driven by economic incentives rather than high-quality evidence—as exemplified by proton-beam radiation, recently found markedly inferior to far less-expensive alternatives. Another study found promise for focal treatment, but much research is required before this could become a standard option.

Of three randomized trials testing lenalidomide maintenance in myeloma, a survival benefit is apparent in one. An increased risk of second cancers is seen in all three trials. Maintenance must be considered after a review of risks and benefits, but it is premature to recommend lenalidomide maintenance for all patients.

Multimodal organ-sparing treatment strategies have shown similar survival rates when compared to radical surgery for muscle-invasive bladder cancer; however, up to 80% of surviving patients retained their own, well-functioning bladder. Within an interdisciplinary bladder-preserving treatment protocol, concurrent chemoradiotherapy was superior to radiotherapy alone—supporting its use as an alternative to radical cystectomy.

Gliomas in children differ from their adult counterparts by histological grade, site of presentation and rate of malignant transformation. Molecular profiling experiments on adult high-grade glioma have revealed key biological differences between the adult and paediatric disease. The authors summarize the current and historical data, compare and contrast the findings in these tumours across age groups, and discuss the implications for paediatric patients whose treatment options are modelled on clinical data from adult patients.

Cancer and its associated treatment cause debilitating symptom clusters including sickness, nausea, fatigue, pain, distractibility and poor memory. The authors of this Review describe what is known about the mechanisms of the behavioural comorbidities experienced by cancer patients, discuss how cancer-related symptoms develop, and what can be done at the clinical and preclinical levels to better understand their mechanisms and identify appropriate treatments.

Neuroblastoma is a debilitating disease and a leading cause of childhood cancer deaths. The discovery of ALK as a mutated oncogenic receptor in neuroblastoma has provided an attractive target for innovative therapies. In this article, Mosse and Carpenter review the preclinical and clinical advances in ALK-targeted therapies for neuroblastoma and discuss the emerging challenges.