It's in this context that consistent reporting and sharing of results (with respect to both diseased and normal tissue) come into their own. How else can the oncologist, the clinical support team and increasingly the patient make informed choices with respect to key metrics like relative safety, quality of life and, most important of all, clinical efficacy.

For comparisons on safety and quality-of-life issues, the central problem is one of data management (or manageability). Traditional safety-reporting methods, for example, are overwhelmed by the amount of toxicity data generated in cancer treatment programmes. Clinical trials in oncology yield mountains of "adverse-event" data, all of which needs to be summarized in order to highlight the headline findings. Things get even more complicated for multimodality trials involving radiotherapy and chemotherapy, chiefly because there's currently no uniform method for summarizing adverse-event data into a concise statement of overall risk.

With this in mind, Andy Trotti of the H Lee Moffitt Cancer Center at the University of South Florida (Tampa, FL) and colleagues in the US have devised a new reporting system (called TAME) for summarizing the toxicity burden of different cancer treatments (Lancet. Oncol. July issue; early publication online DOI:10.1016/S1470-2045(07)70144-4). TAME works by consolidating traditional adverse-event data into three risk domains: short-term (acute) toxicity (T), adverse long-term (late) effects (A), and mortality risk (M). These are calculated for each treatment programme to generate an end-result (E) summary index.

The big advantage of TAME is that it enables formal comparisons of overall toxicity for the first time. Trotti himself describes TAME as "an innovation in reporting", one that assigns treatments into risk classes for each risk domain and in turn identifies trends and patterns that were previously unrecognized.

Revisiting the data

The development of TAME stems from a re-analysis of adverse-event data (including mouth sores, skin reaction, swallowing difficulty, nausea and blood counts) taken from five consecutive phase II and III clinical trials of patients with head and neck cancer. Carried out between September 1991 and August 2000, these trials were managed by the Radiation Therapy Oncology Group (RTOG, a multicentre North American research collaboration sponsored by the US National Cancer Institute) and involved 2304 patients and 13 treatment groups. For RTOG, the purpose of the programme was to evaluate progressive intensities of treatment, including standard (once a day) radiotherapy fractionation, altered fractionation regimens, single-agent concurrent chemoradiotherapy and multiagent concurrent chemoradiotherapy.

Trotti and his co-workers initiated a two-step assessment of the RTOG trial data. In the first part of the work, they carried out a forensic evaluation of an established method for summarizing adverse events (the so-called max-grade method). Next they calculated TAME summary metrics for the same patient groups and compared relative T values with relative values for toxic effects from the max-grade approach.

What they found is that the traditional methods for summarizing adverse events systematically exclude important data, giving an inaccurate impression of the toxicity burden in complex multimodality trials. In contrast, they claim that TAME uses data on all high-grade adverse events, such that the reporting provides a more complete portrait by which to compare relative risk among treatment options.

So how does the radiation oncology team stand to gain from TAME? "Instead of comparing the individual rates of nausea or infection or diarrhoea, we can consolidate the most clinically important event data into a concise statement about overall risk," Trotti explained in an email to medicalphysicsweb. "It means that for the same head and neck patient, one treatment approach may be 200-500% more acutely toxic than another. No-one expected to see 500% - a fivefold difference. Even the head and neck experts were surprised to see that."

He continued: "It is important to know the rates of individual side-effects, but TAME gives you the big picture of toxicity burden, which is driven by the multiplicity of events."

Right now, though, TAME still has some way to go before it can be applied routinely to support clinical decision-making. Studies are needed to assess the system's performance when applied by other research groups to other disease sites. In fact, this process of independent evaluation is already under way. A Danish cancer consortium called DAHANCA has tested the acute T-metric in TAME and confirmed that it serves to quantify overall toxicity burden in more than 2000 patients in its head and neck database. RTOG researchers are also planning to test TAME in multicentre lung-cancer trials.

It's evident that TAME introduces entirely new concepts and the way it is used will no doubt evolve over time. Trotti, for his part, is happy to assist investigators who want to try TAME in their own databases. "In the next few years," he added, "I could speculate that it [TAME] may begin to influence the design of multimodality trials, and perhaps how clinicians and patients make treatment selections."