Radiotherapy following chemotherapy reduces the risk of cancer progression in people with early-stage favorable Hodgkin’s lymphoma, regardless of an individual’s response to chemotherapy, results of a Phase 3 study show.
These findings support the importance of consolidation radiotherapy — which appears to prevent potential cancer relapse or progression — even in patients with complete responses to chemotherapy.
Final results of the Phase 3 HD-16 trial were presented at the 2019 American Society for Radiation Oncology (ASTRO) meeting, held recently in Chicago, in a presentation titled “PET-Guided Treatment of Early-Stage Favorable Hodgkin Lymphoma: Final Results of the International, Randomized Phase 3 Trial HD16 by the GHSG.” The trial results also were simultaneously published in the Journal of Clinical Oncology.
The current standard of care for early-stage favorable Hodgkin’s lymphoma — stage 1 to 2 without risk factors — is a combined-modality treatment (CMT) with two cycles of AVBD chemotherapy regimen followed by involved-field radiotherapy (of 20 Gy).
Previous research had hypothesized that early-stage Hodgkin’s patients showing complete responses to chemotherapy — assessed through positron emission tomography (PET) scans after the second cycle of chemotherapy — might be able to skip radiotherapy.
Now investigators sought to determine whether omitting consolidation radiotherapy would maintain therapy effectiveness.
The multi-center, double-blind, randomized, Phase 3 study, known as HD-16 (NCT00736320), evaluated whether skipping consolidation radiotherapy was a safe strategy for people with early-stage favorable Hodgkin’s lymphoma responding to chemotherapy and with negative PET scans.
Treatment effectiveness was assessed by the time a patient lived without signs of disease progression — a measure called progression-free survival (PFS).
The German Hodgkin Study Group (GHSG) recruited a total of 1,150 people, ages 18 to 75, who were newly diagnosed with early-stage favorable Hodgkin’s lymphoma, from clinical centers in Germany, Switzerland, Austria, and the Netherlands.
The participants were randomly assigned to two groups, of 575 patients each, and followed for a median of 45 months.
The first group received CMT regardless of PET scan results. The second group received PET-guided treatment, in which — after chemotherapy — patients would only be given radiotherapy if they showed positive PET scans.
PET positivity was defined as a Deauville score of three or higher — from a scale of one to five, in which five indicates the most positive scan, and thus, the poorest treatment response.
Among patients with negative PET scans, 328 were treated with CMT (first group), while 300 received chemotherapy alone (second group). After chemotherapy, a significantly higher percentage of participants receiving radiotherapy (93.4%) had no disease relapse or progression within five years after treatment, compared with those who did not receive radiotherapy (86.1%).
Researchers noted that most relapses in participants treated with chemotherapy alone occurred within areas that would otherwise have been covered by radiotherapy.
The study found no differences in terms of toxicity between patients who received or did not receive radiotherapy. The researchers said that shows that the benefits of maintaining consolidation chemotherapy are greater than the risks.
“In early-stage favorable [Hodgkin’s lymphoma], radiation therapy cannot be safely omitted from standard CMT without a clinically relevant loss of tumor control in patients with negative PET-2,” the researchers said.
When evaluating the potential of PET scan results to predict patients’ outcomes, the researchers found that — among all patients treated with CMT — PET positivity was associated with poorer five-year progression-free survival (88.4%) than negative PET scans (93.2%).
When PET positivity was defined as a Deauville score of four or higher, the five-year PFS difference was even greater, with 80.9% of patients with positive PET scans showing no disease progression, compared with 93.1% of those with negative PET scans.
The team added that, in these patients, “a positive PET [scan] after two cycles ABVD indicates a high risk for treatment failure, particularly when a Deauville score of 4 is used as a cutoff for positivity.”
These findings also suggest that people with Deauville scores of four or higher in their PET scans after chemotherapy may need a more aggressive treatment than radiotherapy.