Articles in 2018

Chimeric antigen receptor (CAR) T cell therapies have impressive activity in the treatment of cancer but are associated with potentially fatal toxicities. In light of the approval of CAR T cell therapy for paediatric patients, a panel of experts from the Hematopoietic Stem Cell Transplantation (HSCT) Subgroup of the Pediatric Acute Lung Injury and Sepsis Investigators (PALISI) Network, the CAR T Cell Therapy-Associated Toxicity (CARTOX) Program at The University of Texas MD Anderson Cancer Center, and several other institutions have developed consensus guidelines for the use and management of these treatments in paediatric patients, which are presented herein.

Molecular profiling studies are providing novel insights into the biology of hepatocellular carcinoma, although these remain to be translated into novel effective therapies. Nevertheless, therapeutic advances have been made in the past few years, and further advancements are expected in the near future, including biomarker-driven treatments and immunotherapies, as discussed in this Review.

A recent clinical trial of a virotherapy approach, consisting of an engineered poliovirus, has provided evidence of apparently durable responses in patients with recurrent glioblastoma. The results of this trial and others indicate that virotherapy might be an effective tool in anticancer immunotherapy. Yet, caution must be exercised until appropriately powered randomized clinical trials truly show efficacy.

The majority of patients receiving immunotherapy do not respond to treatment but might still have adverse events. Furthermore, some patients with an initial response will develop acquired resistance to treatment. In this Review, the authors describe the role of circulating tumour DNA in the management of patients receiving immunotherapy.

Comprehensive molecular characterization of infant medulloblastoma has uncovered the high degree of heterogeneity of this disease. Recent results from the SJYC07 study elegantly reveal that risk stratification can be improved if DNA methylation profiling data are incorporated into clinicopathological criteria. Importantly, the delineation of disease subgroups potentially has major clinical implications.

Platinum-based chemotherapy has long been the mainstay first-line therapy for patients with non-small-cell lung cancer without a targetable driver mutation, but has limited effectiveness. Immunotherapy is drastically changing the treatment landscape for this group and improving survival outcomes, with focus turning to frontline immunotherapy combinations.

Accelerated approval enables investigational drugs to reach the US market on the basis of their demonstrated effects in unvalidated surrogate measures, only reasonably likely to predict clinical response. To fulfil the social compromise, regulators should ensure that confirmatory trials testing clinically meaningful end points are already underway at the time of approval.

Liquid biopsy approaches hold great promise in early cancer diagnosis or minimal residual disease monitoring for cancer recurrence. Herein, the authors evaluate contemporary next-generation sequencing approaches to circulating tumour DNA detection in these contexts, with a focus on studies in patients with non-small-cell lung cancer. They discuss the feasibility of introducing these strategies into the clinic, highlighting the technical and analytical challenges, as well as possible solutions.

CARMENA, a trial comparing the efficacy of sunitinib alone to that of nephrectomy followed by sunitinib in patients with primary metastatic renal cell carcinoma who require targeted therapy has demonstrated the non-inferiority of systemic therapy alone. The data provided by this and other studies argue for a lesser role of surgery in the management of these patients.