The landscape of cancer treatment has become increasingly complex in recent decades, with a growing number of therapeutic options and sequences available to clinicians. However, this advancement hasn’t been matched by a standardized system for defining and tracking these treatments, creating challenges for comparing clinical trials and utilizing real-world research data.
To address this issue, the European Society for Medical Oncology (ESMO) has published EnLiST, a consensus-based framework designed to establish a standardized system for defining and enumerating lines of therapy in solid tumors. This development aims to improve consistency and clarity in oncology research and patient care.
Methods
The development of this consensus involved extensive consultation with a wide range of experts, including clinical oncologists, clinical trial investigators, regulatory officials, academics, pharmaceutical industry representatives, clinical research organizations, real-world data and digital health specialists, artificial intelligence professionals, patient advocates, health economics experts and bioethicists. This broad input was crucial to creating a framework applicable to diverse clinical scenarios.
The process unfolded in multiple phases, utilizing the Delphi methodology. Each proposed element was put to a vote among the specialists, requiring a minimum of 75% consensus for approval. Elements failing to reach this threshold were revised, and revoted. The rigorous process aimed to ensure broad agreement and validity of the proposed standards.
Researchers similarly evaluated the framework’s applicability using specific clinical scenarios across different tumor types. A questionnaire was distributed to ESMO members to assess the acceptability of the proposed recommendations. This step helped to refine the guidelines based on practical feedback from practicing oncologists.
Key Proposals of the Guideline
The central goal of the guideline is to establish a uniform vocabulary for defining, counting, and recording lines of systemic therapy in solid tumors. The framework categorizes lines of therapy based on clinical scenario: early-line of treatment (eLoT) for disease in the initial stages, advanced-line of treatment (aLoT) for more progressed disease, and investigational-line of treatment (iLoT) consisting solely of experimental agents.
Each line of therapy is represented by two numbers separated by a decimal point (X.Y). The first number indicates the total number of recent lines of therapy a patient has received, while the second number reflects modifications within the current line. A change in treatment due to disease progression or inadequate response constitutes a new line of therapy, incrementing the number to the left of the decimal (e.g., 1.0 → 2.0).
Conversely, changes made for other reasons – such as intolerance, the addition of another drug to the regimen, or logistical issues – are classified as modified lines, incrementing the number to the right of the decimal (e.g., 1.0 → 1.1). Certain adjustments, like dose modifications, schedule changes, or planned discontinuation of an agent, remain classified as the same line of therapy.
The framework also defines a minimum dataset for recording lines of therapy and provides practical guidance for its application in various clinical settings. This standardization could improve the accuracy and comparability of data across studies and clinical practice.
Considerations
EnLiST addresses a critical need in the rapidly evolving field of oncology, where the number of treatments and clinical trials is expanding exponentially. The structured approach and numbering system could facilitate data analysis, particularly with the increasing utilize of artificial intelligence.
However, the effectiveness of EnLiST will depend on its adoption in real-world clinical practice, which requires endorsement and encouragement from oncology societies and journals, especially when submitting new clinical trials. Standardizing how treatment lines are defined and tracked has the potential to accelerate research and improve patient outcomes.
