Articles in 2019

Despite promising responses in a minority of patients with cancer, considerable scope remains to improve the efficacy of both immune-checkpoint inhibitors and epigenetic drugs, with one potential strategy involving the combination of these two types of treatment. Here, the authors describe the mechanisms underlying the synergy between immune-checkpoint inhibitors and epigenetic drugs and discuss the ongoing clinical development of such combinations.

In the past few years, efforts have been made to combine two approaches — immune-checkpoint inhibition and locally ablative radiation therapy — to treat patients with metastatic non-small-cell lung cancer. Herein we discuss the implications of two studies that support the existence of a systemic therapy augmented by radiotherapy (STAR) effect in this setting.

The presence and prognostic relevance of the intratumoural microbiota in pancreatic cancer, and the roles of intratumoural bacteria in oncogenesis and therapeutic response are beginning to be elucidated. The feasibility of characterizing intratumoural microbial communities from paraffin-embedded tissues has now been validated, providing greater opportunities for retrospective research. Prospective studies are also needed to test the efficacy of rational approaches combining microbial modulation with chemotherapy and/or immunotherapy.

Oncology phase I trials have been traditionally referred to as ‘toxicity trials’. The distinction of clinical trials into three phases has been challenged in the past few years, leading to the current situation in which response rates are increasingly reported from phase I trials. The authors dissect the ethical dilemmas surrounding the therapeutic intent of phase I trials and provide evidence of contemporary phase I trials as a therapeutic option for patients with cancer.

Many argue that phase I cancer trials are a therapeutic option for eligible patients. I question this position and offer a more nuanced view that differentiates between types of trials. Patients seeking treatment might legitimately pursue phase I trials, although labelling all phase I trials as therapeutic contradicts the spirit of evidence-based medicine.

The authors of this Perspective critically evaluate various artificial intelligence (AI)-based computational approaches used for digital pathology and provide a broad framework to incorporate these tools into clinical oncology, discussing challenges such as the need for well-curated validation datasets, regulatory approval and fair reimbursement strategies.

Attempts to incorporate additional criteria into the traditional tumour-node-metastasis staging classification have often resulted in inaccuracy and confusion in the use of terminology. In this Position paper, the authors provide guidance on the consistent use of the terminology relating to cancer staging.

The FDA grants Accelerated Approval when deemed necessary to address an unmet need, with a promise that post-marketing research commitments will be fulfilled and that the approvals will be revisited and eventually changed if clinically meaningful results are reported. Herein, we present a timeline of all Accelerated Approvals granted to immune-checkpoint inhibitors to illustrate three ways in which the FDA has failed to fulfil their part in this social contract.

The majority of patients with cancer have at least one chronic health condition at the time of diagnosis. Nonetheless, how such conditions influence the timeliness of diagnosis remains largely unknown. In this Review the authors describe the available evidence on the complex relationships between cancer and other chronic diseases, and the implications for diagnosis and screening programmes.

Five randomized trials have been conducted to prove that shorter duration of trastuzumab treatment (9 weeks or 6 months) can replace the standard duration (1 year). The results of PERSEPHONE, the most recent trial, suggest that the efficacy of a 6-month treatment is non-inferior to that of 1 year, although not for all patients. We discuss these results in the context of current treatment standards.