PET scans in early-stage Hodgkin’s lymphoma may help guide therapy [RAPID trial]

1. In patients with negative PET scans after 3 cycles of chemotherapy, 3-year progression free survival was slightly better among those who received radiotherapy than among those who received no further treatment, though prognosis was excellent in both groups.

2. Overall survival at 3 years was equivalent between the two groups.

Evidence Rating Level: 1 (Excellent)          

Study Rundown: Treatment of early-stage Hodgkin’s lymphoma traditionally involved chemotherapy combined with radiotherapy. However, the toxic effects of these treatments have led to a shift towards reduced treatment intensity where possible. The Randomised Phase III Trial to Determine the Role of FDG–PET Imaging in Clinical Stages IA/IIA Hodgkin’s Disease (RAPID) trial investigated whether positron emission tomography (PET) scanning after 3 cycles of chemotherapy could be used to guide whether further treatment was needed.

Patients with negative PET scans after 3 cycles of chemotherapy were randomized to receive either radiotherapy or no further treatment. 3-year progress-free survival was slightly higher in the group that received radiotherapy than the group that received no further treatment (94.6% vs. 90.8%, P=0.16). The pre-specified non-inferiority threshold of a 7 percentage point difference between the two groups was not met (-3.8 percentage points, 95% CI -8.8 to 1.3).

Despite this result, the trial did demonstrate that even with no further treatment, 3-year progression-free survival and overall survival were very good (90.8% and 99.0%, respectively). Furthermore, overall survival may be the more relevant outcome to consider when radiotherapy itself may cause lethal complications. Longer-term follow-up will be needed to determine whether long-term overall survival is better without radiotherapy.

Click to read the study, published today in NEJM

Click to read an accompanying editorial in NEJM

Relevant Reading: Reduced treatment intensity in patients with early-stage Hodgkin’s lymphoma; Prognostic value of interim FDG-PET after two or three cycles of chemotherapy in Hodgkin lymphoma

In-Depth [randomized controlled trial]: Four hundred and twenty patients with negative PET scans after 3 cycles of doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) chemotherapy were randomized to receive either 30 Gy of involved-field radiotherapy or no further treatment. PET scans were interpreted at a central location.

RAPID was designed as a noninferiority trial with a noninferiority margin of 7 percentage points. The trial was designed to have 90% power to exclude a 7 percentage point difference at a 5% level of significance with 46 events. However, only 40 events were recorded, meaning that the trial was slightly underpowered.

The intention-to-treat analysis and per-protocol analyses were similar in that both demonstrated better 3-year progression-free survival with radiotherapy rather than no further treatment (intention to treat: 94.6% vs 90.8%; per-protocol: 97.1% vs. 90.8%). There were more deviations from protocol in the radiotherapy group, with 20 patients declining radiotherapy. Only 2 patients in the no further treatment group received radiotherapy.

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