Involved field radiotherapy versus no further treatment in patients with clinical stages IA and IIA Hodgkin lymphoma (HL) and a negative PET scan after 3 cycles ABVD. Results of the UK NCRI RAPID trial


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John Radford1, Sally Barrington2, Nicholas Counsell3, Ruth Pettengell13, Peter Johnson4, Jennie Wimperis5, Stewart Coltart6, Dominic Culligan7, Andrew Lister8, Eric Bessell9, Anton Kruger10, Bilyana Popova3, Barry Hancock11, Peter Hoskin12, Tim Illidge1, Mike O'Doherty2
1The University of Manchester and The Christie NHS Foundation Trust, Manchester, UK, 2PET Imaging Centre, St Thomas' Hospital, London, UK, 3Cancer Research UK and UCL Cancer Trials Centre, London, UK, 4University of Southampton, Southampton, UK, 5Norfolk and Norwich University NHS Foundation Trust, Norwich, UK, 6Kent and Canterbury Hospital, Canterbury, UK, 7Aberdeen Royal Infirmary, Aberdeen, UK, 8Barts and the London School of Medicine, London, UK, 9Nottingham City Hospital, Nottingham, UK, 10Royal Cornwall Hospital, Truro, UK, 11University of Sheffield, Sheffield, UK, 12Mount Vernon Cancer Centre, Northwood, UK, 13St George's, University of London, London, UK

Background

In the RAPID trial PET response directed therapy was evaluated in early stage HL. Patients (pts) received 3 cycles ABVD followed by a PET scan. If the PET scan was ‘negative' (score 1 or 2 on 5 point scale) at central review, pts were randomised between IFRT and no further treatment (NFT). If ‘positive' (score 3, 4 or 5) pts had a 4th cycle ABVD and IFRT. This non-inferiority trial required 400 PET negative pts to be randomised for exclusion of a ≥7% difference in 3-year progression-free survival (PFS).

Method

602 pts with previously untreated stages IA/IIA HL and no mediastinal bulk were registered 2003-2010. Following 3 cycles ABVD, 571 pts had a PET scan of which 426 (74.6%) were ‘negative'. 420 PET ‘negative' pts were randomised to receive IFRT (n=209) or NFT (n=211). 22/209 pts randomised to IFRT did not receive this because 16 pts declined after they became aware of the randomisation decision, 5 had died, 1 had pneumonia.

Results

After median follow-up of 45.7 months, 384/420 (91.4%) PET negative pts are alive/progression-free, 29 (6.9%) are alive/progressed and 7 (1.7%) have died; combined 3-year PFS 92.2% and overall survival (OS) 98.3%. In the IFRT arm, 194 pts are alive/progression-free, 9 have progressed, and 6 have died. In the NFT arm 190 pts are alive/progression-free, 20 have progressed, and 1 has died. 3-year PFS is 93.8% (IFRT) versus 90.7% (NFT) and 3-year OS 97.0% (IFRT) versus 99.5% (NFT). For the 145 PET positive pts, 126 are alive/progression-free, 11 progressed, and 8 died to give a 3-year PFS of 85.9% and OS of 93.9%.

Conclusion

Pts with early stage HL and a negative PET after 3 cycles ABVD have an excellent prognosis without further treatment. This approach reduces treatment time/costs, improves tolerability and removes toxicity of radiotherapy from the PET negative population.