News & Views

Randomized controlled trials designed to test cancer therapies often fail to clarify effectiveness in real-world settings. Herein, we explore lessons for trial development in oncology that can be learnt from the large-cohort, pragmatic RECOVERY trial involving patients hospitalized with COVID-19.

We argue that the evidence remains insufficient for use of intraoperative radiotherapy (IORT) in women with early stage breast cancer outside of a clinical trial, as the recently reported TARGIT-A trial does not provide sufficient evidence to conclude that IORT is superior to no radiotherapy.

Tumour-associated antigens are an attractive therapeutic target in immuno-oncology. Here, the exploratory analyses of T cell responses and preliminary clinical outcomes of the Lipo-MERIT trial of a melanoma vaccine are discussed in the context of prior efforts to harness the immunogenicity of such antigens for antitumour immunity.

A role for extracellular vesicles and particles (EVPs) as cancer biomarkers has been elusive. A mass spectrometry-based comparative analysis of EVPs from individuals with or without cancer has now enabled the identification of tumour-associated protein profiles in EVPs in plasma and paired tumour tissues, validating the role of EVPs as a novel liquid biopsy approach in cancer diagnosis.

Measuring the methylation status of cell-free DNA (cfDNA) in plasma holds great potential for the early, noninvasive detection of cancer. Two recent papers published in Nature Medicine showcase the successful application of cfDNA methylation-based cancer detection to two highly challenging scenarios.

SABR-COMET was the first randomized controlled trial to demonstrate an overall survival benefit with the use of stereotactic ablative body radiotherapy (SABR) for the treatment of oligometastatic cancer. Considering the recently reported long-term follow-up data from SABR-COMET, we review the outcomes and limitations of this study in the context of other emerging information on therapy for oligometastatic disease.

Cell-free DNA and proteins are secreted into the bloodstream by multiple types of cancer. In a recently published prospective study involving 10,006 women, such markers were used in a cancer screening approach that incorporated PET–CT as a confirmatory test. Herein, we discuss the implications of these results.

Lung cancer screening is currently based only on low-dose CT scans; however, novel, more accessible methods that might improve uptake and adherence are eagerly awaited. New liquid biopsy approaches promise to revolutionize cancer screening. Herein, we discuss the opportunities and challenges associated with two such novel assays.

Mature results of the PROfound study demonstrate that the poly(ADP-ribose) polymerase (PARP) inhibitor olaparib prolongs progression-free survival compared with second-generation hormonal therapies in men with metastatic castration-resistant prostate cancer harbouring BRCA1, BRCA2 or ATM mutations. However, a closer look at the efficacy of olaparib on a gene-by-gene basis suggests that its activity is most pronounced in BRCA2-mutant prostate cancers and might not be equally active in all homologous recombination repair-deficient cancers.

Bacteria within tumours affect progression and response to therapy; in addition, bacterial DNA can be detected in cell-free plasma. Herein, we discuss evidence showing that intratumoural bacteria are characteristic for each tumour type, and that detection of cell-free bacterial DNA in blood could provide an accurate and non-invasive test for cancer diagnosis.

Effective anticancer therapies typically activate antitumour immunity, predominately mediated by T cells in the tumour microenvironment. Here, we discuss the roles of B cells and tertiary lymphoid structures in the context of chemotherapy-induced complement activation, which results in the induction of a B cell subset that modulates T cell function.

Evidence of quality of life improvements in patients with advanced-stage cancer has spurred a move towards early integration of palliative care into the outpatient setting. As discussed herein, meaningful and sustained improvements in timely access to palliative care requires commitments to funding, encouraging integration and routinizing referral across care settings. More palliative medicine training positions as well as broader education of clinicians and the public about the benefits of palliative care throughout the disease course are also needed.

The identification of individuals carrying cancer susceptibility genetic variants could be improved by peridiagnostic cancer genetic testing and cascade testing of the relatives of patients diagnosed with cancer. Herein we discuss two studies that highlight the importance of active involvement of the medical team, both in informing the relatives and offering pre-test telephone genetic counselling.

The survival outcomes of the FLAURA trial support osimertinib as the new first-line standard of care for patients with EGFR-mutated advanced-stage non-small-cell lung cancer in health-care systems that can afford its cost. However, the low crossover rate is a flaw of this study. Knowledge of mechanisms of resistance to provide tailored treatment is the new challenge preventing a continued paradigm shift in this disease.

Developing novel technologies to discriminate malignant tissue from nonmalignant structures and thereby facilitate safe, complete tumour resection is a major priority for advancing oncological neurosurgery. Herein, we discuss a recently reported innovation involving stimulated Raman spectroscopy of intraoperative tissue samples and data interpretation with artificial intelligence, as well as the implications of this approach for neurosurgical oncology.

In 2018, the SOLO1 trial set a new standard of care with maintenance olaparib substantially extending progression-free survival (PFS) in women with newly-diagnosed BRCA1/2-mutated advanced-stage ovarian cancer. Herein, we summarize trials of first-line poly(ADP-ribose) polymerase (PARP) inhibition beyond BRCA1/2 mutations, including combination strategies, and discuss the optimum use of PARP inhibition in advanced-stage ovarian cancer.

Liu et al. report data from the largest sequencing analysis of tumour material from patients with metastatic melanoma receiving immune-checkpoint inhibitors. These data confirm the correlations between baseline immune infiltrate and treatment response, but also demonstrate inconsistent associations of tumour mutational burden, specific gene mutations and previously described gene expression patterns with clinical outcomes.

Interval invasive breast cancers diagnosed after a normal mammogram but before the next screening examination have a different tumour biology from that of screen-detected breast cancers, and thus are not detected on mammography. Understanding the genetics and biology of interval invasive cancers could inform better approaches to detection.

The CHECKMATE-227 trial of nivolumab and ipilimumab presents a potential new frontline chemotherapy-sparing treatment option for patients with PD-L1-positive non-small-cell lung cancer and perhaps, in the future, also for those with PD-L1-negative disease. Indeed, the true predictive value of PD-L1 as well as tumour mutational burden remains to be determined, as neither biomarker segregates clearly with responsiveness.

Numerous neoepitope-based vaccination strategies are in testing for clinical use in the treatment of cancer. Rapid identification of immunostimulatory neoantigen targets hastens neoantigen vaccine development. Papers recently published in Nature Biotechnology describe two independent machine-learning-based algorithms that demonstrate improved identification of MHC class II-binding peptides. Herein, we outline the benefits of these algorithms and their implications for future immunotherapies.