A recent study published in Blood confirmed the importance of radiotherapy (RT) among pediatric patients with early‐stage low-risk classical Hodgkin lymphoma (cHL) who had a positive interim PET response after 1 cycle (PET1) of AVPC (doxorubicin, vincristine, prednisone, and cyclophosphamide) chemotherapy. The sites of relapse among these patients suggests the need to further optimize therapy with alternative upfront systemic therapy or intensified radiotherapy at the relapse sites.

“[The Children’s Oncology Group trial AHOD0431 examined whether reducing upfront treatment in early-stage, low‐risk cHL] by using a response‐based approach with minimal initial chemotherapy and omission of involved‐field radiotherapy (IFRT) in [patients with complete response (CR)] could maintain overall survival and event‐free survival (EFS) while reducing late toxicity,” the researchers wrote in their report. “The investigators found that a slow early response (SER) at the first [PET scan after 1 cycle] was prognostic for outcomes and associated with significantly worse EFS in the absence of IFRT despite having a [CR] at the end of chemotherapy.”

In the present analysis, the researchers assessed the impact of PET1 and IFRT on outcomes and relapse pattern in patients on AHOD 0431 who underwent PET1 response assessment after AVPC (ClinicalTrials.gov Identifier: NCT00302003).


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They defined “rapid early response” (RER) as a negative PET1 and “slow early response” (SER) as a positive PET1. Patients with a partial response (PR) by CT and functional imaging following 3 chemotherapy cycles received 21-Gy IFRT, while patients with CR received no IFRT. The investigators evaluated progression-free survival (PFS) for the patients with RER and SER treated with or without IFRT. They also assessed recurrence sites (initial, new, or both) and characterized relapses involving initial sites as those “within PET1+ site” or “initially involved but outside PET1+ site”.

A total of 222 patients who underwent PET1 assessment and, if positive, a subsequent PET3 assessment were included in the current analysis. The median follow-up duration was 118 months. The PET1 response assessment indicated 54% of patients had RER and 46% had SER. Relapse occurred in 18% of patients. Both patients with and without relapse had a median age of 15 years. For all relapses, the median time to relapse was 10.02 (range, 4.11‐32.39) months. For patients with RER, it was 10.83 months in those who did not receive RT and 6.57 months in those who received RT. For patients with SER, it was 8.46 months in those who did not receive RT and 21.40 months in those who received RT.

At baseline assessment, patients with SER were more likely to be female (P =.032) and have stage II disease (P =.0017), an erythrocyte sedimentation rate >20 (P =.0001), and 3 or more sites of disease (P =.0052).

The researchers found that the 10-year PFS rate among patients with RER was 96.6% with IFRT and 84.1% without IFRT (P =.10), while among those with SER, it was 80.9% with IFRT and 64.0% without IFRT (P =.03). A total of 14 relapses occurred among 90 patients with RER who did not receive IFRT, and all of these relapses included an initial site. A total of 16 relapses occurred among 45 patients with SER and received no IFRT, 14 of the 16 (88%) relapses were in the initial site (9 PET1+ site only). A total of 10 relapses occurred among 58 patients who received IFRT, 5 of the 10 (50%) relapses were in the PET1+ site.

“Following 3 cycles of AVPC alone, patients [with RER] experienced favorable results. Conversely, patients [with SER] experienced unfavorable outcomes with AVPC alone, although they improved with 21‐Gy IFRT,” concluded the authors. “Radiotherapy remains an important component of treatment for patients who [have SER].”

Limitations of the study included the exploratory nature, which did not reflect specific upfront planned endpoints, and the small sample size in some subgroups.

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 June 28, 2022.  Blood. doi:10.1182/blood.2022016098