Reviews & Analysis

Perioperative chemotherapy is the standard of care for localized gastric cancer (GC). In 2018, additional postoperative radiotherapy was found to be ineffective; although, docetaxel was found to be superior to epirubicin in perioperative three-drug chemotherapy regimens. Validated biomarkers are needed for benefit from immunotherapy in advanced-stage GC. Metachronous GC can be prevented by Helicobacter pylori eradication.

The first-in-human study of anti-CD47 antibodies blocking CD47–SIRPα interactions in combination with rituximab in patients with non-Hodgkin lymphoma shows encouraging clinical responses accompanied with mild levels of toxicity. Inhibition of the CD47–SIRPα interaction might provide a generic method of promoting the effects of antitumour antibodies in a variety of cancer types. This reveals, for the first time, an innate immune checkpoint as a bona fide target for therapy.

Breakthrough findings reported in 2018 provide the foundations for paradigm shifts in the care of patients with ovarian cancer. These results have implications for treatment in the first-line setting (with improved and refined use of established treatment modalities), firmly introduce concepts of consolidation and maintenance therapy, and enable more accurate prediction of drug sensitivity and resistance.

Women with early-stage oestrogen receptor (ER)-positive (ER⁺) breast cancer remain at risk of distant recurrence for at least 15 years after discontinuation of 5 years of standard endocrine therapy. The authors of this Review discuss the epidemiology and mechanisms underlying late recurrence and examine several models used for risk prognostication and for estimating the presence of minimal residual disease.

Herein, advances in our understanding of the genomic landscape of childhood acute lymphoblastic leukaemia (ALL), encompassing both somatic and germline alterations, are reviewed. The clinical implications of these alterations, particularly those in the germ line, are discussed with regard to susceptibility to ALL, treatment responses and therapy-related toxicities.

In 2018, advances in the treatment of non-small-cell lung cancer (NSCLC) have been observed both in trials of immunotherapies and targeted agents, leading to dramatically improved options for patients with metastatic and stage III NSCLC.

In 2018, the results of multiple phase III trials in metastatic renal cell carcinoma (mRCC) were presented. A phase III noninferiority trial demonstrated the importance of careful patient selection before cytoreductive nephrectomy. Additionally, three randomized phase III trials demonstrated the superiority of combination therapy with an immune-checkpoint inhibitor backbone versus sunitinib in patients with treatment-naive mRCC.

The mechanisms of resistance to immunotherapy seem to broadly overlap with the immunoediting process whereby cancers evade detection by the immune system. The authors of this Review discuss these interactions as well as the strategies that can be used to overcome therapeutic resistance

Patients with cancer might be at a higher risk of nonmedical opioid use than was previously thought; however, opioid analgesics remain the gold standard to treat cancer-related pain. The authors of this Review examine the role of opioids in cancer-related pain, the risk of substance use disorder and methods to achieve the right balance between both to ensure safe opioid use.

Most cancer-related deaths are attributable to metastasis, but few treatments are specifically designed to disrupt this process. In this Position Paper, representatives of the joint Cancer Research UK and Cancer Therapeutics CRC Australia Metastasis Working Group describe the challenges associated with discovering and developing anticancer agents designed specifically to prevent or delay the metastatic outgrowth of cancer and provide guidance on how these challenges might be overcome.

Precision medicine approaches to the treatment of cancer are largely reliant on genomic analysis alone. In this Perspective the authors provide a rationale for the incorporation of analysis of the proteome, which is a rich source of biological heterogeneity, into the treatment and management of patients with cancer.

Integrating molecular nuclear imaging in clinical research has great potential to improve anticancer therapy, particularly through the development of imaging biomarkers. Herein, the multistage process of developing novel molecular imaging biomarkers is discussed, highlighting both the challenges that have restricted the use of molecular imaging in clinical oncology research and future opportunities in this area.

The International Society of Paediatric Oncology (SIOP)–Paediatric Oncology in Developing Countries (PODC) Collaborative Wilms Tumour Africa project delivered treatment in eight centres across five countries in sub-Saharan Africa. Setting up a collaboration like this is easier said than done, and herein we share the lessons we learned along the way.

Broad population screening of asymptomatic individuals for cancers of the prostate or thyroid has resulted in overdiagnosis and overtreatment. Herein, the authors describe the epidemiology, pathology, and screening guidelines for the management of patients with those cancers, and discuss existing international active surveillance protocols.

Many clinical trials are testing the safety and/or efficacy of combining radiotherapy with immunotherapy, nearly all using a single-site irradiation (or ‘abscopal’) approach, but emerging evidence suggests that this approach likely produces suboptimal results. The authors of this Perspective provide a biological rationale supporting the abandonment of the abscopal approach, and instead advocate exploring comprehensive irradiation of multiple/all lesions.

In a cohort of 100 patients with neuroendocrine cancer, the use of NETest enabled earlier prediction of tumour progression and resulted in a reduction in the frequency of follow-up procedures. These outcomes are exciting and promising, but limited in value by the heterogeneity of the study cohort and by suboptimal assay sensitivity and specificity.

FGFR alterations can be detected in a small subset of many different cancer types. Inspired by the successes with other targeted therapies, preliminary attempts to target FGFR-altered cancers have been hampered by low response rates and acquired resistance. In this Review, the author describes the development of FGFR inhibitors thus far, and provides guidance on future research priorities.

A deterioration of disease can occur upon treatment with anti-PD-1/PD-L1 monoclonal antibodies; this paradoxical phenomenon is defined as hyperprogression. The authors discuss the pathophysiological hypotheses that might explain hyperprogressive disease and the resulting challenges for patient management, with a focus in clinical decisions involving immune-checkpoint inhibitors.

Inhibition of poly(ADP-ribose) polymerase (PARP) is the paradigmatic example of synthetic lethal therapy and is predicated on exploiting DNA repair deficiencies that are a hallmark of cancer. In this Review, the authors review the progress made to date with PARP inhibitors and describe the expanding landscape of novel anticancer therapies targeting the DNA damage response. Potential predictive biomarkers, mechanisms of resistance and combinatorial strategies are discussed.

Successful surgical resection offers patients with pancreatic cancer the best chance of survival. However, many patients do not have surgically resectable disease. In this Review, the authors describe recent improvements in pancreatic cancer surgery, which have increased survival and also enabled more patients to undergo surgery.