Despite its associated toxicities, radiotherapy continues to offer significant benefits for pediatric and adolescent patients with early-stage, low-risk classical Hodgkin lymphoma (cHL) who had a positive interim positron emission tomography (PET) response following one cycle (PET1) of AVPC (doxorubicin, vincristine, prednisone, and cyclophosphamide) chemotherapy, according to research findings published in Blood.
Corresponding author Bradford S. Hoppe, MD, of Mayo Clinic Florida in Jacksonville, explained that patients with low-risk pediatric Hodgkin lymphoma (HL) have high rates of cure with first- or second-line therapy and are expected to survive 60 years or more, thereby necessitating the development of strategies that minimize late effects of treatment in this patient population.
“While radiotherapy has predominantly been blamed for most of the late effects in early-stage pediatric and adult HL,” he said, “we need to understand that it was in an era of radiotherapy where we used huge fields and much higher doses to those large fields.”
The analysis by Dr. Hoppe and colleagues focused on data from The Children’s Oncology Group trial AHOD0431. In this trial, investigators evaluated whether the reduction of up-front treatment in patients with early-stage, low-risk cHL with a response-based approach and minimal initial chemotherapy, as well as elimination of involved radiotherapy, could maintain survival with complete response while reducing late toxicity.
Dr. Hoppe and researchers assessed the effect of PET1 and involved-field radiotherapy (IFRT) on outcomes and relapse patterns “in an effort to inform future radiotherapy dose and field design.”
A total of 222 patients in AHOD0431 underwent PET1 response evaluation following AVPC. Those who had a negative PET1 were characterized as “rapid early responders” (RER; 54%), and those with a positive PET1 were classified as “slow early responders” (SER; 46%).
Investigators administered 21‐Gy IFRT following three chemotherapy cycles in patients with a partial response, but complete responders did not receive IFRT. The researchers evaluated progression‐free survival (PFS) for RER and SER patients who received treatment with or without IFRT.
The median follow‐up of the analysis was 118 months. In the RER patients, the 10-year PFS rates were 96.6% with and 84.1% without IFRT (p=0.10). The 10-year PFS rates in the SER population were significantly higher with versus without IFRT (80.9% vs. 64.0%; p=0.03).
Approximately 18% of patients (n=41) experienced a relapse. All 14 relapses in the 90 RER patients who did not receive IFRT included an initial site. In the 45 SER patients who received no IFRT, 14 of 16 relapses were observed in the initial site (nine PET1+ site only), while five out of 10 relapses in the 58 patients who received IFRT were in the PET1+ site.
“The SER site is not only a prognostic factor for higher risk of relapse but also the site of likely relapse,” Dr. Hoppe noted. “One can try and overcome it with more intensive chemotherapy; however, another strategy could be more intensive local treatment, such as a boost in the radiotherapy dose to 30 Gy.”
According to Dr. Hoppe, goals of HL trials should focus on reducing the risk of late effects without eliminating radiotherapy.
“Other treatments, such as auto transplant and anthracyclines, have their own risk of toxicities,” he added, “and novel therapies, such as immunotherapies and drug-antibody conjugates, do not have the follow-up to rule out potential for late effects.”
A limitation of the study was that the analysis was exploratory in nature and does not “reflect specific up-front planned endpoints,” researchers noted. Dr. Hoppe added there is a need to answer whether interim PET-positive disease predicts sites of relapse in patients with more advanced-stage disease.
Any conflicts of interest declared by the authors can be found in the original article.
Reference
Parekh A, Keller FG, McCarten KM, et al. Targeted radiotherapy for early-stage low-risk pediatric Hodgkin lymphoma slow early responders: a COG AHOD0431 analysis [published online ahead of print, 2022 Jun 28]. Blood. doi: 10.1182/blood.2022016098.
