Reviews & Analysis

The development and implementation of more effective genome analysis technologies has enabled substantial improvements in our understanding of the genomic changes that take place in patients with acute lymphoblastic leukaemia (ALL). This Review provides a detailed summary of advances in our understanding of the genomics of ALL, and describes how these advances might lead to improved patient outcomes.

Patient-reported outcome (PRO) measures, such as quality of life, have been associated with relevant clinical end points and are prognostic for survival outcomes in a variety of solid cancers in adults. The authors of this Review comprehensively assess the correlation of PROs with treatment response and survival, and explore tumour-related and patient-centric composite end points in patients with cancer participating in clinical trials.

Two recently published studies provide state-of-the-art evidence on the varying pace of improvement in survival across different cancers, and regarding inequalities in cancer survival between countries and regions. These studies offer rich and contrasting data that can guide policy priorities and research initiatives, and showcase the need for further development of population-based cancer surveillance across the globe.

Since February 2012, the FDA has identified widespread infiltration of counterfeit bevacizumab into the US drug-supply chain. This Perspectives uses this case study to highlight the continued lack of information, knowledge, and solutions necessary to protect patients against future breaches in the drug-supply network, as well as the need for collaborative efforts to enhanced surveillance for counterfeit medicines and improve communication of risk information.

High-risk human papillomavirus (hrHPV) types cause cervical cancer. Hence, a negative hrHPV test provides excellent reassurance against cervical precancer and cancer, superior to a negative cervical smear (Papanicolaou or Pap) test. Screening first for hrHPV might improve the accuracy and positive predictive value of secondary Pap testing in hrHPV-positive women, and thus guide decisions on what care is needed.

The standard treatment for advanced-stage ovarian cancer is upfront cytoreductive surgery, and the extent of residual disease after surgery correlates with response to adjuvant therapy and disease outcomes. This Perspectives article provides an overview of the historical progression of primary cytoreduction and definitions of 'optimal' residual disease. In addition, approaches to personalizing surgical therapy and improving the quality of surgical care are discussed.

Modern genomics technologies enable the identification of genetic alterations, even those present at a low frequency, and can contribute to unveiling the mechanistic rationale behind the unexpected clinical response of 'exceptional responders'. This approach will drive the identification of molecular biomarkers that can be integrated into clinical trials and predict response to a specific therapy.

The evolutionary biology of cancers and organismal species are similar: in both cases, a genetically diverse population mutates and evolves through natural selection. In addition, driving both species and cancers to extinction is extremely difficult. Nevertheless, greater than 99.9% of species that have lived on Earth are now extinct, and the parallels between tumours and organismal evolution suggest that understanding species extinction through paleontology could teach us much about how to eradicate cancers. In this Review, the selective pressures that have driven species extinct and the characteristics of species that make them resistant to extinction are described, and how these factors can be translated to cancers in order to develop improved approaches to therapy and prognosis is discussed.

Current guidelines recommend up to 5 years of follow-up assessment for patients with localized renal cell carcinoma treated by nephrectomy; however, the recommendations are supported only by low-level evidence, and a recent study suggests considerably prolonged follow up is needed. Thus, approaches to follow-up imaging assessments and their actual benefit on disease outcome require further clarification.

Locally advanced breast cancer (LABC) constitutes a heterogeneous entity that includes advanced-stage primary tumours, cancers with extensive nodal involvement and inflammatory breast carcinomas—inoperable cancers with an unfavourable prognosis. The optimal management of LABC requires a multidisciplinary approach consisting of a well-coordinated treatment schedule and close cooperation between medical, surgical and radiation oncologists. In this Review, the authors discuss the current state of the art and possible future treatment strategies for patients with LABC.

A number of breast lesions that are associated with an increased risk of breast cancer and/or represent true precursors of breast tumours are increasingly detected in population screening programmes. At present, the clinicopathological and molecular characteristics that defined the risk of breast cancer in women with these lesions are unknown; nevertheless, management strategies ranging from active surveillance to surgery with adjuvant radiotherapy and endocrine therapy can be planned based on the risk of breast cancer at the population level. Herein, the contemporary approaches to the diagnosis and management of high-risk breast lesions are comprehensively reviewed.

Substantial improvements in the outcomes of patients with multiple myeloma have created a need for more sensitive diagnostic tests for minimal residual disease (MRD) in this patient population. This Review describes and compares the validity of current clinically used tests for MRD, and highlights the significantly improved outcomes of patients who are known to be MRD negative. Possible opportunities and challenges to the clinical use and widespread implementation of highly sensitive MRD testing are discussed.

Debate continues regarding the benefit of primary tumour resection for patients with asymptomatic metastatic colorectal cancer; the largest observational study conducted to date has demonstrated prolonged survival, but was probably subject to biases, and data from previous meta-analyses of observational data are contradictory. The results of two ongoing randomized trials are eagerly awaited. In the meantime, treatment should be directed at symptom palliation.

The routes and timing of metastatic dissemination during cancer progression remain shrouded in mystery. However, phylogenetic studies are beginning to shed new light on this process and various models have been proposed. In this Review, Kamila Naxerova and Rakesh Jain discuss the hypothesized trajectories of metastasis, and examine the extent to which the current phylogenetic evidence support these models. In addition, the experimental techniques of lineage tracing, their strengths and weaknesses, and future directions for studies using such methods are discussed.

The use of image-guided ablation techniques—including radiofrequency and microwave ablation, cryoablation, and irreversible electroporation—is increasing, predominantly in the treatment of small hepatic and renal tumours (<5 cm). This Review describes the technical considerations for the various ablation modalities. In addition, the authors review the evidence that supports the clinical application of these minimally invasive techniques for the treatment of liver and kidney cancers, and discuss their potential as the standard-of-care first-line treatment, particularly for small, early stage tumours.

The perioperative timeframe is pivotal in determining long-term cancer outcomes. This Review covers the various aspects of surgery which could facilitate the metastatic process. Through understanding these processes and reviewing empirical evidence, the authors provide suggestions for potential new perioperative interventions aimed at attenuating deleterious processes and improving treatment outcomes. The measures described in this Review could transform the perioperative timeframe from a prominent facilitator of metastatic progression, to a window of opportunity for arresting and/or eliminating residual disease.

In 2014, no major breakthroughs were made in understanding the biology of breast cancer or its management; few novel practice-changing studies were presented or published. Nevertheless, important negative results from studies that challenge some of the current concepts, particularly in drug development, underline 2014 as a year of 'failed surrogates and precocious expectations'.

Heterogeneity within and across tumours is increasingly recognized as a critical factor that limits therapeutic progress for many cancers. Key studies reported in 2014 describe previously unappreciated patterns of geographical and temporal heterogeneity for glioblastoma (the most-common primary CNS tumour in adults), with important implications for ongoing therapeutic studies evaluating molecular targeted therapies.

The results of several clinical trials in metastatic colorectal cancer presented in 2014 will influence clinical practice. These findings include definitive data from phase III trials comparing bevacizumab and cetuximab-based therapy in the first-line, studies elucidating the value of maintenance therapy after induction treatment, and data on new agents in this disease.