No abstract

Tumours respond differently to immunotherapies compared with chemotherapeutic drugs, raising questions about the assessment of changes in tumour burden—a mainstay of evaluation of cancer therapeutics that provides key information about objective response and disease progression. A consensus guideline—iRECIST—was developed by the RECIST working group for the use of modified Response Evaluation Criteria in Solid Tumours (RECIST version 1.1) in cancer immunotherapy trials, to ensure consistent design and data collection, facilitate the ongoing collection of trial data, and ultimate validation of the guideline. This guideline describes a standard approach to solid tumour measurements and definitions for objective change in tumour size for use in trials in which an immunotherapy is used. Additionally, it defines the minimum datapoints required from future trials and those currently in development to facilitate the compilation of a data warehouse to use to later validate iRECIST. An unprecedented number of trials have been done, initiated, or are planned to test new immune modulators for cancer therapy using a variety of modified response criteria. This guideline will allow consistent conduct, interpretation, and analysis of trials of immunotherapies.

The Response Evaluation Criteria in Solid Tumors (RECIST) were developed and published in 2000, based on the original World Health Organization (WHO) guidelines first published in 1981. In 2009, revisions were made (RECIST 1.1) incorporating major changes, including a reduction in the number of lesions to be assessed, a new measurement method to classify lymph nodes as pathologic or normal, the clarification of the requirement to confirm a complete response (CR) or partial response (PR) and new methodologies for more appropriate measurement of disease progression. The purpose of this paper is to summarize the questions posed and the clarifications provided as an update to the 2009 publication.

Imaging biomarkers (IBs) are integral to the routine management of patients with cancer. IBs used daily in oncology include clinical TNM stage, objective response and left ventricular ejection fraction. Other CT, MRI, PET and ultrasonography biomarkers are used extensively in cancer research and drug development. New IBs need to be established either as useful tools for testing research hypotheses in clinical trials and research studies, or as clinical decision-making tools for use in healthcare, by crossing ‘translational gaps’ through validation and qualification. Important differences exist between IBs and biospecimen-derived biomarkers and, therefore, the development of IBs requires a tailored ‘roadmap’. Recognizing this need, Cancer Research UK (CRUK) and the European Organisation for Research and Treatment of Cancer (EORTC) assembled experts to review, debate and summarize the challenges of IB validation and qualification. This consensus group has produced 14 key recommendations for accelerating the clinical translation of IBs, which highlight the role of parallel (rather than sequential) tracks of technical (assay) validation, biological/clinical validation and assessment of cost-effectiveness; the need for IB standardization and accreditation systems; the need to continually revisit IB precision; an alternative framework for biological/clinical validation of IBs; and the essential requirements for multicentre studies to qualify IBs for clinical use.

2-[ 18 F]Fluoro-2-deoxyglucose positron emission tomography (FDG-PET) assesses a fundamentalpropertyof neoplasia, theWarburgeffect.This molecularimaging technique offers acomplementary approach to anatomic imaging that is more sensitive and specific in certain cancers. FDG-PET has been widely applied in oncology primarily as a staging and restaging tool that can guide patient care. However, because it accurately detects recurrent or residual disease, FDG-PETalso has significant potential for assessing therapy response. In this regard, it canimprove patient management by identifying responders early, before tumor size is reduced; nonresponders could discontinue futile therapy. Moreover, a reductioninthe FDG-PETsignal withindays or weeks of initiating therapy (e.g., in lymphoma, non^small cell lung, and esophageal cancer) significantly correlates with prolonged survival and other clinical end points now usedin drug approvals.These findings suggest that FDGPETcould facilitate drug development as an early surrogate of clinicalbenefit.This article reviews the scientificbasis ofFDG-PETandits development andapplicationasavaluableoncologyimagingtool. Its potential to facilitate drug development in seven oncologic settings (lung, lymphoma, breast, prostate, sarcoma, colorectal, and ovary) is addressed. Recommendations include initial validation against approved therapies, retrospective analyses to define the magnitude of change indicative of response, further prospective validation as a surrogate of clinical benefit, and application as a phase II/III trial end point to accelerate evaluation and approval of novel regimens and therapies. FDG-PET (2-[18 F]Fluoro-2-deoxyglucose positron emission tomography) is an accepted and widely used clinical imaging tool in oncology. U.S. Medicare reimbursement of FDG-PET recently expanded to encompass all cancer patients participating in certain prospective studies or registries in addition to more general coverage in 10 defined oncologic settings. Primarily covered are disease diagnosis, staging, and restaging, but FDG-PET is also approved for monitoring response to therapy in locally advanced and metastatic breast cancers when a change in therapy is anticipated. Clinical trials in breast cancer and other settings [e.g., non -small cell lung cancer (NSCLC) and esophageal cancer] have shown that FDG-PET imaging can provide an early indication of therapeutic response that is well correlated with clinical outcome. FDG-PET thus has the potential to improve patient management, particularly by signaling the need for early therapeutic changes in nonresponders, thereby obviating the side effects and costs of ineffective treatment. As an early surrogate for clinical benefit, the modality also has the potential to facilitate oncologic drug development by shortening phase II trials and detecting clinical benefit earlier in phase III investigations. Studies to further explore and validate these approaches are needed and can be conducted in parallel with those employing end points now use...