Review Articles in 2014

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.

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.

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.

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 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.

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.

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.

Recent studies of neuroblastoma have shed light on the dramatic heterogeneity in its clinical behaviour, which spans from spontaneous regression or differentiation to relentless disease progression. This Review describes the different mechanisms of spontaneous neuroblastoma regression—including neurotrophin deprivation, humoral or cellular immunity, loss of telomerase activity and alterations in epigenetic regulation—and the consequent therapeutic approaches, as a better understanding of these mechanisms might help to identify optimal therapies.

Advancement of an investigational therapy into the adjuvant and/or neoadjuvant settings without clear evidence of efficacy in metastatic disease is exceptional; however, this course is being followed in the clinical investigation of poly(ADP-ribose) polymerase (PARP) inhibitors, owing to their potential benefit for a well-defined subset of patients with tumours defective in homologous recombination. This Review provides a bench-to-bedside overview of PARP inhibitor therapy, and an update on the current status of the clinical development of such agents.

The landscape of translational oncology has shifted dramatically over the past 10 years, characterized by the introduction of more-sophisticated molecular tools into the clinic and advances are being employed in genomic clinical trials that will examine the feasibility of matching a broad range of systemic therapies to specific molecular tumour characteristics. The authors review selected developments in translational cancer biology, diagnostics, and therapeutics that have occurred over the past decade and offer our thoughts on future prospects for the next few years.

Immunoconjugates are specific, effective, minimally toxic anticancer therapies. They allow the delivery of a range of different effectors, including pharmacologic agents, radioisotopes, and toxins, to cancer cells. Of note, highly cytotoxic anticancer molecules could be linked to specific antibodies, which mask the toxic effects of the drug until it reaches its target. This Review summarizes the successes and shortcomings of immunoconjugates, and discusses the future potential for these therapies.

Delirium is a common neurocognitive manifestation in patients with cancer, particularly at advanced stages of the disease, and represents a considerable challenge for the patients, their families as well as health-care professionals involved in their care. This Review provides a comprehensive overview of the diagnosis, assessment, pathogenesis and management of delirium. The experiential impacts of delirium on patients with the condition, their family members and health-care practitioners are also discussed.

Lymphoma represents a heterogeneous disease both across and within histological subtypes. The future for the treatment of patients with lymphoma will involve matching a targeted therapy to the unique genetic and molecular composition of each lymphoma. This Review discusses biomarkers that can guide treatment decisions for patients with lymphoma, and explore the challenges and strategies for making biomarker-driven personalized medicine a reality in the cure and management of this disease.

Antiangiogenic therapies are cytostatic rather than cytotoxic and, therefore, do not simply decrease tumour sizes. Thus, traditional assessment of radiographic response according to MRI-based tumour-volume criteria can no longer be considered adequate. Instead, vessel-calibre MRI has emerged as a potential alternative—providing insight into vessel type and oxygenation status, and opening possibilities for clinical trial design and monitoring therapeutic response and outcomes.

Fatigue is one of the most common adverse effects of cancer that might persist for years after treatment completion. Among the biological mechanisms underlying cancer-related fatigue, inflammation processes have a key role in the development and persistence of this symptom. In addition, genetic, biological, psychosocial, and behavioural risk factors are also associated with the occurrence of cancer-related fatigue. This Review describes the mechanisms, risk factors, and possible interventions for cancer-related fatigue.

The treatment options available for hepatocellular carcinoma (HCC) vary depending on prognostic factors that include tumour characteristics and clinical status, particularly with regard to liver function. This Review discusses the links between disease phenotype, prognosis and therapy, focusing on the subclassification of patients with intermediate-stage HCC following the BCLC staging system, who are usually ineligible for curative resection and ablation treatments or liver transplantation; the therapies that are available for this patient subgroup are described.

Active immunotherapy is emerging as an important addition to conventional cancer treatments, but many important questions remain. Optimal combinations of antigens, adjuvants and delivery vehicles need to be determined and effective strategies for overcoming tumour-associated immunosuppression ought to be developed. This Review provides an overview of new results from clinical studies of therapeutic cancer vaccines directed against tumour-associated antigens and discusses their implications for the use of active immunotherapy.