Oncology imaging plays a significant role in the evaluation of tumor response to investigational therapeutic compounds. Response Evaluation Criteria in Solid Tumors (RECIST v1.1) is a standardized, validated set of guidelines used in oncology research to evaluate the activity of novel cancer therapies on solid tumors. Response can be categorized as complete response (CR), partial response (PR), stable disease (SD), or progressive disease (PD), based on changes in tumor size and disease burden over the treatment period. While RECIST is widely accepted as providing a recognized framework for oncological assessment, it has its limitations, leading to the recognized value of quantitative imaging biomarkers such as volumetric analysis, functional imaging, and the assessment of radiomic features.

While RECIST provides data based on linear measurements combined with qualitative disease assessments, quantitative imaging biomarkers offer earlier insights on response, tumor metabolism, proliferation, and cellularity which cannot be captured by RECIST alone. RECIST, while recognized by regulatory agencies as a standardized and validated framework, can be complemented by novel response assessment methods and quantitative imaging biomarkers, particularly in cases where traditional size-based criteria may be insufficient. This article will consider how oncology imaging is evolving towards quantitative biomarkers, considering what this looks like in practice, and how an imaging CRO with a long lasting proven track record in oncological clinical trials can enhance effective integration.

Evaluation of RECIST

RECIST combines the precise, quantitative measurements by radiologists of target lesions with the subjective judgment of non-target lesions, new lesions, and overall imaging interpretation. New lesions always indicate progression, as long as those are unequivocally related to the primary tumor, and the guidelines dictate how decreases from baseline and increases from the nadir determine treatment response. While RECIST is a validated instrument and the reference standard for evaluating the efficacy of solid tumor therapeutics, it has come under fire throughout the medical community regarding its reliability and clinical relevance.

RECIST is not organ-specific, not treatment-specific, and in some cases, may fail to recognize certain treatment-induced changes, meaning some patterns of response or progression cannot be documented. For example, cases of immunotherapy pseudoprogression, tumor flare reactions, cystic or necrotic transformation, mixed or heterogeneous response, or non-size-based changes such as metabolic response, can complicate interpretation and potentially lead to the misclassification of treatment outcomes. RECIST interpretation, therefore, requires specialist reader experience and may also need an oncologist’s input to determine the actual impact of an investigational therapy. In response to such concerns, quantitative imaging biomarkers are under increasing exploration, helping researchers to capture biologic and functional tumor changes that cannot be evaluated through size alone.

It is important to note that while RECIST may have its limitations, the scientific basis for drugs that have been approved using a RECIST-based surrogate endpoint remain valid.

Quantitative imaging biomarkers

A quantitative imaging biomarker can be defined as “an objectively measured characteristic, derived from a medical image, that can be correlated with anatomically and physiologically relevant parameters”. Extracting quantifiable measures from digital imaging has demonstrated immense value in clinical research, particularly for areas of oncology that rely on precise tumor characterization. Quantitative imaging biomarkers provide a more comprehensive understanding of tumor biology and treatment effect, used to enhance overall tumor response assessment, treatment planning, prognostic and predictive biomarker development, early-phase clinical trials, functional and molecular imaging, and longitudinal disease monitoring.

Prominent examples of quantitative imaging biomarkers include standardized uptake values (SUV), apparent diffusion coefficient (ADC), volumetric tumor assessment, perfusion metrics, and the evaluation of radiomic features. These quantitative measures can be geared more accurately towards tumor specific properties, capturing data on metabolism, cellularity, perfusion, hypoxia, heterogeneity, and other tumor specific attributes that influence response to therapy and help to better determine the right subject population most likely to respond to the new treatment.

Practical implications and real-world use

While quantitative biomarkers show promise, yielding favorable reproducibility generally comparable to RECIST, their implementation is widely limited by a lack of standardization and the need for clinical validation. Their use in practice adds value to real-world data, detecting pathologies present in early therapeutic response which could be the difference between clinical trial success and its failure. Quantitative imaging biomarkers require a network of experienced readers and nuanced therapeutic expertise to ensure accurate acquisition and interpretation, and guidelines require rigorous validation to confirm their reliability and clinical relevance for real-world use.

Perceptive Imaging  has a network of experienced readers and years of expertise developing and managing oncology clinical trials. Using state-of-the-art imaging techniques, Perceptive successfully characterizes the behavior of novel therapies and identifies imaging biomarkers across diverse tumor model types. Perceptive has a team of dedicated scientific imaging experts ready to support the implementation and interpretation of quantitative imaging biomarkers throughout the entire lifecycle of your oncology clinical trial.

Learn more about Perceptive Imaging and contact an imaging solutions specialist.

Resources

European Journal of Radiology. What do biomarkers add: Mapping quantitative imaging biomarkers research. https://www.sciencedirect.com/science/article/pii/S0720048X21005337#b0020

Frontiers in Oncology. Twenty Years On: RECIST as a Biomarker of Response in Solid Tumours an EORTC Imaging Group – ESOI Joint Paper. https://www.frontiersin.org/journals/oncology/articles/10.3389/fonc.2021.800547/full