Reviews & Analysis

In 2014, developments in our understanding of escape signalling circuits implicated in resistance to targeted agents in patients with lung cancer have led to improvements in tackling such resistance. The potential role for PET in the management of erlotinib therapy, novel combination therapies and pharmacogenomic-driven individualization of platinum-based chemotherapy represent other key advances.

The classical end points—overall survival, progression-free survival, and response rate—used in cancer clinical trials have important limitations that not only increase the cost and duration of the drug development process, but can also confound establishment of a statistically significant clinical benefit. This Review discusses these issues, and highlights the urgent need for biomarker-based end points, focusing on those that are under investigations in lung cancer, that closely correlate with disease outcomes and that, therefore, hold promise as surrogates for traditional clinical end points.

In 2014, strides were made in the care of haematological malignancies. In particular, the heterogeneity of multiple myeloma was unravelled, and new diagnostic criteria and frontline standards of care were proposed; new therapeutic approaches have been validated and approved in chronic lymphocytic leukaemia; and in chronic myeloid leukaemia, complete cytogenetic response was confirmed as the primary therapeutic end point.

The use of umbilical cord blood (UCB) as source of haematopoietic cell is becoming a mainstay treatment for several diseases. Its principal limitation is the low number of haematopoietic stem and progenitor cells (HSPC), which leads to prolonged engraftment times. The two main approaches to improve UCB engraftment have been to expand HSPCex vivobefore transplantation, or to augment HSPC homing. This Review focuses on approaches and clinical trials aimed at realizing these strategies.

Interventional oncology aims to develop new disease-modifying treatment options beyond conventional surgical and oncological therapies. Clinical investigators should incorporate measures of cost-effectiveness and patient-reported outcomes into large-scale studies to provide robust evidence for changing clinical practice. In particular, interventional oncology trials could be designed to show that certain treatments might be as effective as the current standard of care, but with less morbidity and better outcomes for patients with cancer.

With no large randomized phase III trials to provide definitive answers, the ideal number of platinum-based chemotherapy cycles in patients with advanced non-small-cell lung cancer has long been unclear. Most guidelines recommend a maximum of 4–6 cycles. Rossi and colleagues now suggest that four chemotherapy cycles is the optimal regimen.

The new discipline of interventional oncology, a branch of interventional radiology, involves the treatment of cancer using highly technological image-guided ablation modalities, such as laser, radiofrequency and microwave ablation, cryoablation and electroporation. The roles of these techniques in oncology are not firmly established, although the evidence base is increasing. In this Review, the relationships between interventional radiology and other oncological disciplines are discussed. In particular, the potential benefit of collaboration between the fields of interventional oncology and radiation oncology is highlighted.

Although radiotherapy is a key component of cancer treatment, provision of this modality is not immune to limits placed on health-care expenditure. Recent studies suggest European radiation oncology resources will generally be insufficient to meet future, and in some cases current, needs. This challenge and how it might be addressed is discussed herein.

Recent developments in the treatment of multiple myeloma have led to improvements in response rates and to increased survival; however, relapse is inevitable in almost all patients. Currently, there is no standard treatment for patients with relapsed and/or refractory disease. This Review discusses the current treatment landscape for patients with relapsed and/or refractory multiple myeloma and highlights disease-related and patient-related factors that are important considerations for clinicians when selecting an appropriate treatment.

Biomarkers that predict a patient's responsiveness to anticancer therapies are of increasing importance during drug development and in clinical trials, as well as in the clinic. In this Review, the major challenges to biomarker development and standardization are discussed, and the considerations for validation of the pre-analytical, analytical and post-analytical protocols involved in biomarker assays are highlighted.

The RAINBOW study has demonstrated that ramucirumab plus paclitaxel as second-line treatment for advanced-stage gastric cancer prolongs survival compared with paclitaxel alone. These data confirm that ramucirumab represents a new effective treatment option for gastric cancer. Nevertheless, new treatment options remain eagerly awaited in this disease with dismal outcomes.

The molecular characteristics and clinical outcomes of head and neck cancer vary widely. In this Review, the authors focus on established and emerging biomarkers that are most relevant to nasopharyngeal carcinoma and head and neck squamous-cell carcinoma (HNSCC). Applications and limitations of currently established biomarkers are discussed, and ongoing efforts to shift from prognostic to predictive biomarker development with the goal of delivering individualized cancer therapy is highlighted.

Adoptive immunotherapy using T cells genetically engineered to express a chimeric antigen receptor that targets CD19, a B-cell differentiation antigen, has demonstrated impressive efficacy in a range of B-lymphoid malignancies. The latest results demonstrate the potential of this approach in patients with chemotherapy-refractory diffuse large B-cell lymphoma.

Surgery is the oldest oncological discipline and remains the cornerstone of treatment for most patients with cancer. However, the way surgery is used to treat cancer has evolved and outcomes continue to improve as a result of greater biological understanding, relentless technical innovation and a paradigm shift towards multimodal treatment. In this Perspectives, the authors discuss the developments in cancer surgery that have occurred over time and provide an overview of the key uses of surgery in the current era of multidisciplinary cancer care.

Although most patients with breast cancer have clinically negative axillary nodes at preoperative assessment, 15–20% of these women will have metastatic disease within the lymph nodes at operative sentinel node biopsy. The authors discuss the evidence base for management of the axilla after detection of a positive sentinel node, discuss why micrometastatic disease requires systemic but not axillary therapy, and describe data indicating that axillary irradiation gives equivalent control to axillary node clearance, with less morbidity.

Two large randomized trials have advanced our knowledge of myeloma care. The first study reported that autologous stem-cell transplantation remains the frontline therapy for transplant-eligible patients with multiple myeloma in the current era of novel agents. Together, this study and the second large trial in transplant-ineligible patients demonstrate the value of maintenance treatment with continuous lenalidomide.

The Collaborative Wilms Tumour Africa Project comprises eight centres in sub-Saharan Africa, which are implementing a treatment guideline that has been developed for local conditions. Uniform outcome evaluation, communication and training are all part of the project remit and will ultimately serve to improve cancer care for children in Africa.

Numerous calls for improvement in the quality of follow-up care provided to cancer survivors, particularly survivors of childhood cancer have been issued by key health organizations in the USA; the Passport for Care (PFC) is a web-based support system for survivor care that was developed in response. In this Perspectives, key individuals involved in the development of this support tool for clinical decision making outline the programme, describe how it compares with similar guidance tools, and discuss the potential implications of the PFC for survivorship care. The challenges encountered and the lessons learned during development and deployment of the PFC are also highlighted.

Immunotherapies for cancer are demonstrating increasing success, and efforts are underway to generate and test new immunotherapies in a wider array of paediatric cancers. Mackall and coauthors discuss the emerging science driving this rapidly moving field and highlight the most pressing challenges that must be overcome for continued progress in this arena, including how to optimize management of novel toxicities associated with these agents and how best to incorporate these therapies into standard treatment paradigms.

Medulloblastoma is the most-common form of paediatric brain cancer. Advances in our understanding of the molecular basis of medulloblastoma indicate that it is not a single disease, but a collection of four distinct molecular tumour subtypes. This knowledge has important implications for medulloblastoma research and treatment. In this Review, the characteristic demographic, clinical and genetic features of the four molecular subtypes of medulloblastoma are described, and the implications of molecular distinctions on therapy are discussed.