Diagnosis articles within Nature Reviews Clinical Oncology

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  • News & Views |

    Over the past decade, iterative improvements to models predicting breast cancer risk have primarily come from new information about genetic risk factors and improvements to mammogram-based risk scores. Epigenetic risk factors offer some potential to further improve risk stratification. However, the recently developed DNA methylation score (the WID-BC index) is not yet convincing for predicting breast cancer risk.

    • Melissa C. Southey
    •  & Pierre-Antoine Dugué

  • Review Article |

    PD-L1 expression is currently the best available biomarker for the prediction of responsiveness to immune-checkpoint inhibitors. However, several immunohistochemical assays are now approved for clinical use in various settings, despite imperfect inter-assay concordance, with important implications for pathology services and, potentially, for clinical outcomes. In this Review, the authors compare the performance of the various FDA-approved PD-L1 assays, discuss the varying implications of PD-L1 expression across different tumour types and provide guidance on possible novel approaches that might optimize the clinical utility of PD-L1 as a biomarker.

    • Deborah Blythe Doroshow
    • , Sheena Bhalla
    •  & Fred R. Hirsch

  • News & Views |

    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.

    • Christian Rolfo
    •  & Alessandro Russo

  • Review Article |

    Despite improvements in diagnostic strategies, cancer of unknown primary — metastatic cancer in patients in whom the primary tumour remains undetected — continues to account for around 1–2% of all cancers. In this Review, Rassy and Pavlidis discuss insights into the biology of CUP and shifts in the clinical management of this enigmatic disease entity in the era of precision medicine.

    • Elie Rassy
    •  & Nicholas Pavlidis

  • News & Views |

    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.

    • Michael L. Martini
    •  & Eric K. Oermann

  • Editorial |

    An increasing number of studies suggest that artificial intelligence could revolutionize medicine. In oncology, we are only beginning to fully understand the practical implications.

  • News & Views |

    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.

    • Joshua C. Leinwand
    •  & George Miller

  • Perspective |

    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.

    • Kaustav Bera
    • , Kurt A. Schalper
    •  & Anant Madabhushi

  • Consensus Statement
    | Open Access

    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.

    • James Brierley
    • , Brian O’Sullivan
    •  & Mary Gospodarowicz

  • News & Views |

    In a landmark analysis, investigators of the Multicentric Italian Lung Detection (MILD) trial have confirmed 10-year mortality reductions with lung cancer screening using low-dose helical CT (LDCT). These data complement the reduced lung cancer-specific mortality reported in the National Lung Screening Trial and reinforce the rationale for broad implementation of LDCT screening in high-risk populations.

    • Matthew B. Schabath
    •  & Denise R. Aberle

  • Review Article |

    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.

    • Lisa M. Lowenstein
    • , Spyridon P. Basourakos
    •  & Jeri Kim

  • News & Views |

    Population-based mammographic screening is widely accepted as an intervention to reduce overall mortality from breast cancer, but at the cost of morbidity due to false positives and substantial overdiagnosis and overtreatment of ultra-low-risk disease, as well as personal and health-economic burdens. Recent data from a modelling study strengthen the rationale for personalized, risk-based screening approaches, now being tested in multiple clinical trials.

    • Laura J. Esserman
    •  & Andrea Z. LaCroix

  • Review Article |

    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.

    • Luc Cabel
    • , Charlotte Proudhon
    •  & François-Clément Bidard

  • Perspective |

    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.

    • Christopher Abbosh
    • , Nicolai J. Birkbak
    •  & Charles Swanton

  • News & Views |

    PapSEEK, a novel liquid-based cytology test, enabled the highly specific detection of endometrial and ovarian cancer in a retrospective study. Herein, I discuss potential applications of this tool, both for cancer screening of asymptomatic populations and for the early diagnosis of cancer in symptomatic women.

    • Usha Menon

  • Perspective |

    Despite extensive research efforts, very few DNA methylation-based biomarkers have been implemented clinically. In this Perspective, the authors describe the importance of considering the genomic locations examined in determining the diagnostic or prognostic relevance of putative DNA methylation-based biomarkers.

    • Alexander Koch
    • , Sophie C. Joosten
    •  & Manon van Engeland

  • News & Views |

    Major advances in our understanding of the molecular pathogenesis of non-small-cell lung cancer (NSCLC) have led to effective targeted therapeutics in several genomically-defined subsets of NSCLC. The recently updated College of American Pathologists, International Association for the Study of Lung cancer, and Association for Molecular Pathology joint guideline, which was endorsed by ASCO, sets new standards for molecular testing in NSCLC.

    • Chul Kim
    •  & Giuseppe Giaccone

  • Review Article |

    The development of cancer involves several epigenomic alterations, and the presence of certain alterations before the development of cancer is associated with cancer risk. In this Review, the authors describe the potential of epigenomics-based assays to predict an individual's risk of cancer, including discussions of technical, practical and societal issues regarding the implementation of such assays.

    • Martin Widschwendter
    • , Allison Jones
    •  & Nora Pashayan

  • Comment |

    In 2017, FDA Oncology approved 17 new drug and biologic applications, 32 supplemental drug and biologic applications, and two biosimilar applications in oncology. These actions included landmark approvals of two chimeric antigen receptor T cell therapies and the first site-agnostic, biomarker-defined approval. Three next-generation sequencing 'oncopanels' designed to detect hundreds of somatic genetic aberrations were also approved.

    • Gideon M. Blumenthal
    •  & Richard Pazdur

  • Review Article |

    A wide range of gene fusions have been detected in solid tumours, and the products of these fusions, some of which result in constitutive activation of kinase signalling, can be targeted using tyrosine-kinase inhibitors. However, the development of acquired resistance is almost inevitable. In this Review, the authors describe strategies used to diagnose and treat patients with fusion-positive cancers.

    • Alison M. Schram
    • , Matthew T. Chang
    •  & Alexander Drilon

  • Opinion |

    Accurate detection and monitoring of treatment responses is an essential element of the management of patients with lymphoma. In this Perspectives, the authors describe the evolution of lymphoma staging criteria and highlight unaddressed questions, which, if answered, will substantially improve the management of patients with lymphoma.

    • Joel Cunningham
    • , Sunil Iyengar
    •  & Bhupinder Sharma

  • Opinion |

    Precision medicine has dramatically changed the landscape of drug development in oncology, but this paradigm shift remains to be adopted in early phase clinical trials of molecularly targeted agents and immunotherapeutic agents in children with cancer. The authors, members of the Innovative Therapies for Children with Cancer (ITCC) Consortium, describe trial design strategies to enable drugs with promising activity to progress rapidly to randomized studies and, therefore, substantially accelerate drug development for children and adolescents with cancer.

    • Lucas Moreno
    • , Andrew D. J. Pearson
    •  & Gilles Vassal

  • News & Views |

    Early diagnosis is a key component of melanoma prevention, but diagnostic accuracy varies considerably among clinicians managing patients with potentially suspicious skin lesions. Several tools have been developed to objectively enhance diagnostic assessment and accuracy. Herein, we discuss the potential diagnostic value and limitations of GoogleNet Inception, a new tool for image-based classification of skin lesions.

    • Jeffrey E. Gershenwald
    •  & Kelly C. Nelson

  • News & Views |

    The Cancer Genome Atlas Research Network recently published the most comprehensive, multi-omic molecular characterization of cervical cancers performed to date. The data reveal novel disease subtypes, and provide new insights into the aetiology and pathogenesis of cervical cancer. Importantly, the information obtained has potentially major clinical implications.

    • Chris J. L. M. Meijer
    •  & Renske D. M. Steenbergen

  • Year in Review |

    In 2016, results of an extensive trial broadened the range of malignancies that can be treated with everolimus to include neuroendocrine tumours (NETs) of the lung and gastrointestinal tract. Furthermore, studies aimed at identifying biomarkers with increased specificity, and at better defining high-grade NETs have enabled substantial progress towards delivering effective targeted treatments to patients with NETs.

    • Massimo Falconi
    •  & Stefano Partelli

  • News & Views |

    Molecular cancer-classifier assays enable the diagnosis of a single cancer type for most patients with cancer of unknown primary (CUP), thus opening the door to the administration of site-specific therapies. Herein, I discuss how such therapies can improve the survival of patients with CUP, and the resulting paradigm shift towards tissue-of-origin diagnostics and treatments that is now becoming the standard of care for this patient population.

    • F. Anthony Greco

  • Consensus Statement
    | Open Access

    Imaging biomarkers (IBs) are used extensively in drug development and cancer research, but important differences exist between IBs and biospecimen-derived biomarkers. A tailored 'roadmap' is required for the development of new IBs to be used either in clinical research or for decision-making in healthcare. In this Consensus statement, a group of experts assembled by CRUK and the EORTC present 14 key recommendations for accelerating the clinical translation of IBs.

    • James P. B. O'Connor
    • , Eric O. Aboagye
    •  & John C. Waterton

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