Nicholas Gulati, an assistant professor of dermatology at New York's Icahn School of Medicine at Mount Sinai, has a problem with how the world measures cancer treatment's most visible side effects. In a viewpoint published in JAMA Oncology, Dr. Gulati and his colleagues are calling for a fundamental overhaul of the Common Terminology Criteria for Adverse Events (CTCAE)—the global standard framework that oncologists use to grade and report skin toxicities and other side effects across cancer trials worldwide.
For decades, CTCAE has been the lingua franca of cancer research, the system that allows clinicians and researchers to speak the same language when documenting how patients experience rashes, itching, and other dermatological complications from immunotherapies and targeted cancer treatments. But as newer cancer drugs proliferate and side effect profiles shift, the current version 6.0 of CTCAE has become, in the Mount Sinai team's view, dangerously outdated. The problem is structural: the system grades skin toxicity severity by how a condition is treated—topical cream, oral medication, intravenous therapy—rather than by what the patient actually experiences or how the condition looks clinically.
This disconnect matters enormously. When severity is defined by treatment escalation rather than patient symptoms, the same rash could be graded completely differently depending on which hospital a patient attends or which specialist manages their care. A patient with widespread itching and sleep disruption might receive a lower grade if treated with a subcutaneous biologic—a newer option that CTCAE doesn't adequately account for—than a patient with identical symptoms treated with topical steroids at another institution. The result is inconsistency that ripples through clinical trials, muddying comparisons between drugs and potentially delaying or distorting regulatory approval decisions.
Dr. Gulati and his team, including Thomas U. Marron, a professor of medicine and immunology at Mount Sinai, argue this framework no longer reflects how dermatologists actually diagnose and manage skin conditions. "When severity is defined by treatment approach instead of patient symptoms or disease extent, we risk misclassifying side effects and introducing variability across institutions," Dr. Gulati explains in the paper. The problem has only grown more urgent as immunotherapies and targeted treatments, which frequently cause skin-related side effects, have become central to cancer care.
The Mount Sinai researchers propose a patient-centered alternative. Instead of tying severity to treatment type, they advocate grading based on symptom burden—itching, pain, sleep disruption—combined with impact on daily activities and quality of life, plus the extent of skin involvement, from localized to widespread. This approach would standardize reporting regardless of treatment setting or a prescriber's individual practice patterns, making trial comparisons meaningful and ensuring that real patient experience drives the grading system rather than quirks of regional treatment practice.
The stakes extend well beyond better paperwork. Because CTCAE shapes how new therapies are evaluated and compared globally, improving the framework could enhance cross-trial comparisons, inform clinical guidelines, and—most importantly—ensure that the data reflects what patients are actually living through. The authors call for closer collaboration between dermatologists, oncologists, and the National Cancer Institute in future updates. As cancer therapies become more sophisticated, the way medicine measures their human cost must evolve accordingly.