Researchers in the US have come up with a new way of measuring the relative toxicity of different cancer therapies that could give patients and doctors a much clearer picture of the risks attached to various treatment options.

The team led by Professor Andy Trotti from the H Lee Moffitt Cancer Centre, University of South Florida, describes the TAME system and its significant impact on assessments of relative toxicity burden in the July edition of The Lancet Oncology.

The sheer volume of toxicity data associated with cancer treatments calls for a differential approach to summarising adverse-event reports, the authors argue, commenting: “Traditional safety reporting methods were designed for low-risk, non-cancer treatments, and are simply overwhelmed by the amount of toxicity data generated in cancer treatment programmes.”

Whereas established summary methods only allow treatment-to-treatment comparisons for each type of side-effect and disregard large amounts of potentially important information, the TAME approach includes all types of side-effect and considers their relative frequency, explain Trotti et al. Using a concise grading system, the new method takes a mass of highly complex safety data and focuses on consolidating clinically meaningful events that have high symptom burdens or may compromise the delivery of treatment.

The TAME system groups traditional adverse-event data into three risk domains: short-term (acute) Toxicity (T); Adverse long-term (late) effects (A); and Mortality risk (M). These variables are calculated for each treatment programme to produce an end-result (E) summary index that, the researchers say, provides a “total toxicity price” of the different cancer treatment options available.

Relative T values

In The Lancet Oncology paper, the TAME method was used to analyse five trials conducted with head and neck cancer patients by the Radiation Therapy Oncology Group between September 1991 and August 2000. As a comparison, an established method of summarising adverse events – the max-grade system – was applied to the same five trials, which involved 13 treatment groups and 2,304 patients.

The researchers compared relative T values in these studies with relative values for toxic effects from the max-grade approach. They also calculated the range of individual patient T scores in two groups from one of the trials (the laryngeal-preservation study).

Trotti’s team found that the max-grade method systematically excluded 29% to 70% of total reported high-grade (grades 3-4) acute adverse events, contained progressive bias and favoured higher toxicity programmes. While this method showed differences of 170% between treatment groups in the acute toxicity burden from cancer therapies, with the TAME system the disparities reached nearly 500%.

For the individual patient T scores, four risk classes were designated for acute and late adverse events: low (100-140), moderate (150-390), high (400-490) and extreme (> 500). The distribution of these scores revealed that 82 (60%) patients who received concurrent platinum-radiotherapy for larynx preservation reported two or more high-grade events and 34 (26%) reported four or more high-grade events.

This differed significantly from the distribution of individual T scores with patients who received radiotherapy alone, 32 (19%) of whom reported two or more high-grade events while three (3%) reported four or more high-grade events.

Less variation in relative risk

The max-grade method also systematically excluded 26% to 48% of high-grade late adverse events in the 13 treatment programmes analysed, Trotti et al note. Here, however, less variation (100-270) was detected in the relative risk of late adverse events by the TAME method.

TAME reporting provides “a concise and uniform” method for comparing relative risk among treatment options, the researchers conclude. Future studies, they suggest, should include testing the system’s performance in additional datasets (from different research organisations and disease sites), as well as prospective correlation of TAME endpoints with predefined outcome measures and assessment of the method’s usefulness in clinical decision-making.