Physicians at the Icahn School of Medicine at Mount Sinai are calling for updates to a widely used system that grades side effects from cancer treatments, warning that current criteria may misclassify the severity of skin-related toxicities and limit consistency across clinical trials.
In a Viewpoint published in the May issue of JAMA Oncology , first author Nicholas Gulati, MD, PhD, Assistant Professor of Dermatology and Director of the Oncodermatology Clinic at Mount Sinai, and colleagues outline key limitations in version 6.0 of the Common Terminology Criteria for Adverse Events (CTCAE), the standard framework used worldwide to report side effects in oncology studies. The message is timely as skin-related side effects, such as rashes and itching, become increasingly common, particularly with the rise of immunotherapies and targeted treatments.
The authors, including Thomas U. Marron, MD, PhD, Professor of Medicine (Hematology and Medical Oncology), and Immunology and Immunotherapy, at the Icahn School of Medicine at Mount Sinai, argue that the current system ties severity grades too closely to how a condition is treated, rather than how it affects patients, which can lead to inconsistent reporting and hinder comparisons across studies.
"CTCAE plays a critical role in how we evaluate cancer therapies, but for skin toxicities, the current framework doesn't fully reflect how dermatologists diagnose and manage these conditions today," said Dr. Gulati. "When severity is defined by treatment approach instead of patient symptoms or disease extent, we risk misclassifying side effects and introducing variability across institutions."
While CTCAE version 6.0 introduced some improvements, including more patient-centered criteria for certain conditions, many categories still define severity by the need for, or type of, treatment escalation (for example, topical vs. oral vs. intravenous therapy).
According to the authors, this approach does not align with modern dermatologic practice. Newer therapies, including subcutaneously administered biologics, are now commonly used and may be introduced earlier in the course of treatment—yet the current grading system does not adequately account for these options.
As a result, the same skin condition could be graded differently depending on where a patient is treated or which specialist is involved, creating challenges for clinical trial reporting and regulatory decision-making.
To address these issues, the Mount Sinai team proposes an alternative grading approach that separates severity from treatment type and instead prioritizes patient-reported symptom burden (such as itching, pain, and sleep disruption), impact on daily activities and quality of life, and extent of skin involvement (e.g., localized vs. widespread disease).
Their model is designed to produce more consistent and clinically meaningful assessments, regardless of treatment setting or prescribing patterns.
"Our goal is to move toward a system that better captures what patients are actually experiencing," said Dr. Gulati. "By focusing on symptoms and quality of life, we can improve both the accuracy of reporting and the relevance of the data for clinical care."
Because CTCAE is used across oncology clinical trials worldwide, inconsistencies in grading can affect how new therapies are evaluated, compared, and ultimately approved. The authors note that improving the framework could enhance cross-trial comparisons, inform clinical guidelines, and better reflect real-world patient experiences.
The paper also calls for closer collaboration between dermatologists, oncologists, and the National Cancer Institute in future updates to CTCAE to ensure the system keeps pace with evolving treatment approaches.
"As cancer therapies become more advanced, the way we measure their side effects must evolve as well," Dr. Marron added. "This is an opportunity to build a more accurate and patient-centered standard for the future."
The paper, titled "Cutaneous Toxicities in CTCAE Version 6.0: A Dermatologist's Perspective," is authored by Dr. Gulati, Dr. Marron, and medical students Brandon R. Block and Jaanvi Mehta of the Icahn School of Medicine at Mount Sinai.
Full article: https://jamanetwork.com/journals/jamaoncology/article-abstract/2849432'
