Results of the 2nd Planned Interim Analysis of the RAPID Trial (involved field radiotherapy versus no further treatment) in Patients with Clinical Stages 1A and 2A Hodgkin Lymphoma and a ‘negative’ FDG-PET Scan after 3 Cycles ABVD
Authors: Radford John , O’Doherty Michael , Barrington Sally , Qian Wendi , Patrick Philippa , Coltart Stewart , Culligan Dominic , Wimperis Jennie , Bessell Eric , Linch David , Johnson Peter , Cunningham David , Lister T. Andrew , Hoskin Peter , Pettengell Ruth , Hancock Barry , Illidge Timothy 
Published: April 2020

Abstract
The goal of response adapted treatment in Hodgkin lymphoma (HL) is to maximise the number of cures whilst minimising the effects of late toxicity on the incidence of endocrine dysfunction, infertility, second cancers and cardiovascular disease. In early stage disease abbreviated chemotherapy (CT) followed by involved field radiotherapy (RT) is the current standard of care but some patients (pts) may be cured by CT alone. If it were possible to identify this population, RT and associated toxicity could then be avoided in a proportion of pts using a response adapted approach. 18FDG-positron emission tomography (PET) provides an opportunity to identify pts with an excellent prognosis after CT but the impact on disease control of de-escalating treatment (no consolidation RT) based on these imaging data requires careful evaluation. Here we present results of the 2nd planned interim analysis of an ongoing randomised trial (RAPID) comparing no further treatment with involved field RT following 3 cycles ABVD and a ‘negative’ (-ve) PET scan. Consenting pts with histologically proven, previously untreated HL, stages 1A and 2A above the diaphragm are eligible for trial entry. Following 3 cycles ABVD, responders have a PET scan performed at one of 13 UK imaging centres (all calibrated for quality control purposes by phantom imaging) and if this is reported -ve for HL (score 1 or 2 on a 5 point scale) following central review at the Core Lab in London, pts are randomised between involved field RT and no further treatment. Those with a PET scan ‘positive’ (+ve) for HL (score 3, 4 or 5) have a 4th cycle of ABVD and involved field RT. When 320 PET -ve pts have been randomised the trial is powered to exclude a 10% difference in PFS with 90% power. At the time of analysis in May 2008, 369 pts (190 male, 179 female; median age 34.5 yrs) had been registered since trial activation in October 2003. Following 3 cycles ABVD, 331 have had a PET scan which at central review has been allocated a score of 1 (n=203, 61%), 2 (n=58, 18%), 3 (n=35, 11%), 4 (n=20, 6%) or 5 (n=15, 4%) giving an overall PET -ve rate (score 1 or 2) of 79%. 255 PET -ve pts have been randomised to receive involved field RT (n=125, 49%) or no further treatment (n=130, 51%). 6 pts have not been randomised (pt choice, 2; randomization data entered after database frozen for analysis, 2; clinician choice, 1; error, 1). After a median of 13 months from randomisation, 245 of 255 (96%) pts are alive and progression free, 6 (2%) have progressed and 4 (1.5%) have died (HL, 1; treatment related, 1; other 2). In this the 2nd planned, interim analysis of RAPID, we have shown that designation of PET -ve/+ve status at Core Lab review is feasible and patients are willing to undergo randomisation to answer a de-escalation of therapy question. The PET +ve rate of 21% after 3 cycles ABVD is at the upper end of the expected range and the event rate after short follow-up is very low. Accrual continues with an extended recruitment target of 535 to facilitate exclusion of a 7% difference between the randomised arms. This is based on views obtained from a survey undertaken at the 7th International Symposium on Hodgkin lymphoma (Cologne, Germany, 2007)1
1 Capturing expert opinion at an international meeting (IM) to understand what constitutes a practice changing result in an NCRN clinical trial featuring de-escalation of treatment in Hodgkin lymphoma (HL). Radford J et al, NCRI conference, Birmingham UK, October 2008