Reviews & Analysis

The recently updated HER2 testing guidelines by ASCO and the College of American Pathologists (CAP) are a significant step towards personalized medicine. It is excellent news that such great effort has been put into standardizing biomarker assessment. Undoubtedly, these recommendations will improve the analytical validity of HER2 testing, its clinical utility and the communication among health-care providers.

The international phase III REGARD study demonstrated improved overall survival with ramucirumab as second-line therapy for patients with advanced-stage gastric and gastroesophageal junction adenocarcinoma. As a novel biological treatment, is ramucirumab also the harbinger of a new era of targeted therapies in this prevalent and highly morbid disease?

A landmark study has delineated and identified the genetic pathways that drive the natural course of chronic lymphocytic leukaemia (CLL) B cells into Richter's transformation. CLL-related Richter's transformation is a distinct lymphoma, and poses various questions about B-cell ontogeny and relevance of B cell receptor signalling inhibitors.

Many targeted anticancer treatments may benefit only a subgroup of the histologically-defined population and thus may be missed by traditional randomized clinical trial designs that focus on the overall treatment effect. New biomarker driven designs can help to identify subgroups of patients who are most likely to benefit from these treatments. In this Review the authors discuss how to select appropriate designs and analysis strategies for phase III, biomarker driven clinical trials, using specific examples to illustrate their advantages (and disadvantages).

Chemoprevention has been increasingly explored to mitigate the global burden of prostate cancer and the overtreatment of indolent disease that has arisen in the prostate-specific antigen screening era. In this Review, the authors summarize the major findings of chemoprevention trials and discuss the future opportunities in this arena.

Is there such a thing as a 'good death'? Palliative care services alleviate the debilitating physical symptoms and psychological distress that patients with cancer frequently experience at the end of their lives. In this Review, Khan and colleagues discuss the preferences of these patients and how advance care planning can help in meeting these choices.

Recent immunotherapy approaches have focused on antibodies that block immune checkpoints, and these approaches have produced significant clinical responses in melanoma, lung cancer and kidney cancer. The authors of this Review briefly review the basic immunology underlying an antitumour immune response, and discuss the most relevant clinical trial results in these three tumour types.

Primary care providers are pivotal in reducing diagnostic delay of cancer, particularly in health systems that have long waiting times for outpatient diagnostic services. In this Review, the authors discuss several aspects of primary care, from referrals to communication and follow-up care, focusing on the most common cancers managed at the GP office.

Colorectal cancer (CRC) screening strongly reduces CRC-related mortality, with the effects of screening persisting for 20–30 years. These observations support current CRC screening and surveillance guidelines. At the population level, screening contributes to longer, healthier living. Thus, it is one small step for mankind, yet one giant leap for man.

Diffuse large B-cell lymphoma (DLBCL) is curable in advanced stages, but up to one-third of patients will ultimately fail to respond to initial therapy. As we have now entered the molecular era of defining DLBCL, the goal is to pinpoint driver mutations and pathway addictions within distinct molecular subsets of DLBCL. This Review describes the current molecular understanding of DLBCL and discusses promising targeted approaches for each subtype.

Controversy surrounds the use of mammography for breast cancer screening. This commentary explains why retrospective analyses of women who die from breast cancer do not add to the body of knowledge about the value of screening in young women. Mammographic screening alone cannot be expected to overcome aggressive biology.

Concerns still exist regarding the best use of low-dose CT screening for lung cancer and how to select high-risk individuals who will benefit most from participation in screening programmes. Two studies now indicate factors that may reduce the false-positive rate of lung cancer screening with low-dose CT.

In this Review, the authors describe the pathophysiological effects of chemotherapy and radiotherapy that affect the heart and treatment-related cardiovascular effects in children with cancer. They argue that 5-year event-free oncological survival is no longer the paradigm of successful treatment of childhood cancer; instead overall quality of life is and maximizing oncological efficacy while minimizing toxicity and late-effects should be the ultimate goal.

Biopsy of suspected metastatic lesions is recommended, but not always performed in the clinic. Niikura and colleagues outline the rationale and techniques for performing biopsies on suspected breast metastases. The authors describe the issues surrounding biomarker discordance between primary and metastatic tumours and outline the optimal treatment approach to limit such problems.

A randomized phase III trial comparing pazopanib with sunitinib in patients with advanced clear cell renal cell carcinoma showed that although progression-free survival and overall survival were similar, pazopanib was better tolerated. Recent advances in genomics and metabolomics have provided novel insights that could be leveraged to improve therapy.

Iniparib showed promising results in randomized phase II trials in patients with triple-negative breast cancer; however, negative results from a phase III study in this disease setting, tempered enthusiasm for this agent. The authors of this Review scrutinize the development of iniparib from preclinical studies to registration trials, and identify and discuss the pitfalls in the development of anticancer drugs to prevent future late-stage trial failures.

The survival of patients with multiple myeloma has improved tremendously over the years. However, patients with disease that has relapsed and is refractory to thalidomide, lenalidomide and bortezomib have poor long-term outcomes. The novel immunomodulatory drug pomalidomide now offers a new therapeutic option for these patients.

The treatment of urological cancers is becoming increasingly complex, and, as a result, multiple specialties are required to maximize outcomes. London Cancer is an organisation with the remit of improving outcomes for patients with cancer using multidisciplinary teamwork within a large urban population. Key performance indicators will be used to assess the quality of care, and will ultimately demonstrate improved outcomes.

Establishing breast cancer chemoprevention in standard clinical practice requires advances in many different fields, including biomarker research, the development of more powerful tools to predict and communicate the risks and benefits of treatments and establishing innovative trial designs. In this Review, the authors examine the efforts in breast cancer chemoprevention and explain why the field is progressing slowly than hoped.

There is much concern in the literature over the lack of reproducibility of many scientific reports. In this Perspective, the authors discuss how cognitive biases in research and flaws in the academic incentive system also contribute to the publication of immature results. The authors suggest some changes to the grant submission and funding system that could further improve the reproducibility of research findings.