The study showed impressive preliminary results but only included 40 participants. How scalable might the intervention be if larger studies provide the same positive outcomes?
“I think this is an important approach — many people have been thinking that we should start early interventions to tackle this,” said Hiroto Inaba, MD, PhD, pediatric oncologist and faculty member at St. Jude Children’s Research Hospital in Memphis, Tennessee. “The number of patients involved is small, but I think the important thing is that they started the intervention very early, just after diagnosis and showed that it was feasible, and they got good compliance with the intervention,” added Dr Inaba.
There are several theories as to why obese patients experience more toxicities that may lead to changes in treatment regimens and poorer outcomes. One is that chemotherapy dosage is generally calculated by body surface area, which takes into account weight and height. The other relates to fat causing chronic inflammation that might affect responses to treatment and treatment outcomes in obese patients.
“Some studies show worse outcomes for obese patients and some show no significant difference. But what we do know is obese patients tend to have more toxicities while on treatment, such as infections,” Dr Inaba explained.
The IDEAL trial included patients aged 10 to 21 years, which does not reflect the majority of pediatric ALL diagnoses that typically occur at age 2 to 5 years.
“I think they picked the age range that is easier for the intervention — this is a very good start for our teenagers. But the majority of the ALL population is younger, and they do mention widening the intervention to these patients, too, in their future work,” Dr Inaba continued.
“Patients with leukemia at this age have a much higher incidence of MRD if they’re in the high-risk category. So that gives us a better chance of actually finding an effect of this diet and exercise. Also, childhood obesity is in a way cumulative, especially when these kids hit adolescent years, they get more and more insulin resistance. So, that seemed like a good window where we could intervene and hopefully make a big metabolic change for these kids,” said Dr Mittelman.
The comparison arm to the intervention was an age-matched historical cohort from another study (ClinicalTrials.gov Identifier: NCT01317940). The patients were aged similarly; however, the biological features of the historical cohort, inclusive of cytogenetics, were of a poorer prognosis and suggested that the intervention designed for the IDEAL trial could be even more successful than this preliminary study indicated.
“What I would like to see next is a larger patient number and a randomized trial, if possible. It would also be great to see a larger diversity in age, ethnicity, and even language spoken, as these can all affect compliance and effect of interventions. In the future, perhaps other childhood cancer types can be explored, too,” Dr Inaba proposed.
One aspect of the IDEAL trial that did not provide the hoped outcome was the target to have the patients perform 200 minutes of moderate exercise per week.
“In [the] induction phase, we give patients chemotherapy, which makes them gain body fat, but they’re also going through really hard chemotherapy and so they’re not moving around very much. Promoting exercise was more challenging. It isn’t that the desire wasn’t there; much of the issue was the fact that they just weren’t feeling up for it,” Dr Orgel explained.
For the next trial, the researchers are planning more strategies to help patients increase their activity level, including more supervised exercise time. Larger-scale studies are in the planning stage, and the researchers hope to refine the intervention further to provide even more benefit as well as expanding the age range to include more patients.
“We hoped the intervention would improve outcomes, but we had no idea it would be so effective,” Dr Mittelman concluded. “We can’t really add more toxic chemotherapies to the intense initial treatment phase, but this is an intervention that likely has no negative side effects. In fact, we hope it may even reduce toxicities caused by chemotherapy,” Dr Mittelman added.
- Orgel E, Framson C, Buxton R, et al. Caloric and nutrient restriction to augment chemotherapy efficacy for acute lymphoblastic leukemia: the IDEAL trial. Blood Adv. 2021;5(7):1853-1861. doi:10.1182/bloodadvances.2020004018
- Tucci J, Alhushki W, Chen T, et al. Switch to low-fat diet improves outcome of acute lymphoblastic leukemia in obese mice. Cancer Metab. 2018;6:15. doi: 10.1186/s40170-018-0189-0
- Orgel E, Sposto R, Malvar J, et al. Impact on survival and toxicity by duration of weight extremes during treatment for pediatric acute lymphoblastic leukemia: a report from the Children’s Oncology Group. J Clin Oncol. 2014;32(13):1331-1337. doi: 10.1200/JCO.2013.52.6962