Defining Patient Tolerability to Cancer Treatments Helps Reduce Negative Outcomes


Date Posted, by DCP Staff

NCI’s Cancer MoonshotSM Tolerability Consortium is developing new ways to analyze clinical- and patient-reported data to better understand tolerability of cancer treatment and the patient experience.

For decades, cancer patients have participated in clinical trials of new therapies, and clinicians have assessed and recorded any adverse or toxic reactions to the treatments. Over the years, researchers have standardized the reporting of those side effects using Common Terminology Criteria for Adverse Events (CTCAE).

Three seated female patients who are recovering from cancer therapies: one doing her nails, one reading, and the other crocheting.
Patients who experience side effects from cancer therapies may not finish their treatment, missing a chance for treatment success.

More recently, a new measurement system entitled the Patient-Reported Outcome Common Terminology Criteria for Adverse Events (PRO-CTCAE®) has been developed to work alongside CTCAE. This system allows patients to report side effects from their own perspective.

Assessing the toxicity and tolerability of cancer treatments from the patient’s perspective is critical: Patients who experience side effects from cancer therapies may not finish their treatment, missing a chance for treatment success. Within a clinical trial, those who cannot finish treatment miss the opportunity to provide important results from the trial that may affect the study outcome and inhibit further development of the potentially useful therapies.

Secondly, side effects of trial therapies can have a significant effect on patients’ lives long after the conclusion of their treatments. Researchers and clinicians must take it into consideration when a therapy works well but has negative long-term effects.

NCI’s Cancer Moonshot Tolerability Consortium members seek to better understand and assess cancer treatment tolerability through analysis of clinical trial data and patient-reported data, such as PRO-CTCAE®. Made up of four funded research teams, the consortium includes physicians, biostatisticians, data scientists, investigators with PRO measurement expertise, cancer clinical trialists, and patient advocates.

The initiative deliberately chose to use four diverse teams to focus on specific areas of interest. These teams share their methods to analyze PRO-CTCAE® and other PRO data to understand treatment tolerability and ways to communicate PRO data graphically.

The following briefly describes each team:

Mayo Clinic and University of North Carolina Alliance

This team develops and validates methods to analyze and visualize PRO-CTCAE® results and to standardize useful metrics of tolerability. This includes approaches to missing data; statistical analysis; and graphical representations. These approaches will allow researchers to consider symptoms present before treatment, analyze summary measures, and better visualize adverse event reporting from clinical trials.

Ethan Basch, M.D., M.Sc.; Amylou Dueck, Ph.D.; and Gita Thanarajasingam, M.D., lead this joint effort. They said “We have developed the PRO adverse effects statistical packages to visualize patient-reported adverse event data. This package incorporates our work adjusting for patient baseline symptoms and enabling composite scores for generating clinically relevant summary tolerability metrics.” These packages are available on CRAN and


This team focuses on the trajectories and predictors of early discontinuation of treatment. The goal is to help providers better identify and support patients at risk for treatment discontinuation, dose reductions, and treatment delays.

The ECOG-ACRIN is looking into measuring “bother”—assessed through a tool used to evaluate quality-of-life in people with cancer. The ‘bother’ item is one of 27 items measured in the questionnaire, but can be used as a predictor of whether a patient will discontinue treatment. The team reported that they have demonstrated the importance of collecting patient-rated tolerability information to identify patients at risk for not receiving the full benefit of cancer treatment. For example, patients reporting “I am bothered by this treatment” from the beginning are more likely to discontinue their treatment early in the process.  “Our research points to the importance of patient-centered strategies to measure the tolerability of cancer treatment,” Dr. Robert Gray and Lynne Wagner said.

They are also examining the impact of the cumulative burden of chronic stress and life events, called the allostatic load, on symptom burden.

The University of Rochester

This team uses PRO-CTCAE® data to evaluate treatment tolerability in older patients with advanced cancer and age-related disabilities, comorbidities (sickness other than cancer), and geriatric syndromes. The team developed flow diagrams to help researchers visualize PRO-CTCAE® trajectories, as well as predictive modeling to refine existing models and build new tools, and a cumulative symptomatic toxicity score for older populations.

Supriya Mohile, M.D., M.S.; Marie Flannery, Ph.D., R.N.; and Eva Culakova, Ph.D., noted that NCI Community Oncology Research Program (NCORP) investigators at the University of Rochester collaborated with consortium members, the Cancer and Aging Research Group, and patient advocates to evaluate optimal tools for assessing adverse events in older patients with advanced cancer receiving chemotherapy, a population that is underrepresented in cancer clinical trials.

“We found that patient-reported symptoms and functional status provide important complementary information to traditional measures such as clinician-rated adverse events,” the doctors said. “These findings can be integrated into the design of clinical trials for older patients with advanced cancer.”

Cedars-Sinai Medical Center/University of California-Los Angeles/NRG Oncology

This team developed a new toxicity index to measure the experiences of cancer patients undergoing treatment as assessed by their clinicians. The team used patient-reported outcomes from randomized trials to assess the impact of variables such as age, gender, ability to perform tasks (performance status), and baseline assessments on toxicity and treatment discontinuation.

The team created tools to visualize and explore the tolerability data, including a novel interactive web application that allows investigators to estimate the likely patient-reported and toxicity index outcomes for specific diseases and treatments.

Mourad Tighiouart, Ph.D., of UCLA and Cedars-Sinai, said that the team was able to demonstrate the importance of the toxicity index “in detecting treatment differences in toxicity profiles relative to the traditional average and maximum grade scores.”

What’s Next?

The consortium has identified several priorities for the near future to advance the group’s findings to date. These include:

  • validating the consortium’s tools in different clinical trial data sets;
  • validating the tools in specific populations (i.e., children and adolescents); and
  • incorporating all tools into prospective clinical trials.

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