Volume 11 Issue 12, December 2014

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.

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.

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.

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.

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.

Many cancers, particularly those that arise in childhood, have a hereditary component. In this Perspectives article, the authors provide their views on how the increased adoption of high-throughput DNA sequencing technologies, which produce vast genetic data that is not necessarily limited to known cancer-susceptibility loci, and cancer surveillance strategies are influencing the clinical management of familial cancer. Important ethical issues relating to genetic counselling and disclosure of genetic information on disease susceptibility are discussed, and strategies for approaching these ethical dilemmas are proposed.

In this Viewpoint, four key opinion leaders discuss the slow rate of drug development in paediatric oncology, which must be addressed in a meaningful way if we are to make progress. They discuss a range of aspects, from clinical trial design and biomarker discovery to regulatory amendments and input from industry, government, academia, non-governmental organizations and patient advocacy groups.

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.

In the West, childhood cancers are associated with a very high level of treatment success (approaching 90%), with many childhood survivors reaching adulthood. Perhaps because of this success, progress in the field of paediatric oncology has lagged behind that of adult malignancies. Drug development is slow, and rarely examined in the paediatric population first-hand. Treating the child with cancer brings into play a number of issues not typically experienced with adult patients that can have a range of long-term effects: from dosing infants to performing surgery near growing structures. Paediatric oncology is a bustling field with a wide remit, from genomic studies to surgical innovations. This focus issue aims to look at a number of the key issues, and the cutting-edge research, surrounding treating arguably our most vulnerable patients. Free full access until 1 May 2015