547 In early stage HL abbreviated chemotherapy (ACT) followed by involved field radiotherapy (IFRT) is the current standard of care but some patients (pts) are probably cured by ACT alone. PET imaging has the potential to identify pts with an excellent prognosis after ACT and so provide the opportunity to avoid radiotherapy and reduce late treatment toxicity in these individuals. We present results of the RAPID trial evaluating PET response directed therapy in pts with previously untreated stages I and II HL, no B symptoms or mediastinal bulk. All pts taking part in RAPID received 3 cycles ABVD followed by a PET scan at one of fifteen quality controlled/assured PET Scan Centres across the UK. Acquired images were transmitted electronically to the Core Lab in London for central review. If the PET scan was reported ‘negative’ (score 1 or 2 on a 5 point scale), pts were randomised between IFRT and no further treatment (NFT). Those with a ‘positive’ PET scan (score 3, 4 or 5) 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) from 95% in the IFRT arm, with 90% power and 5% significance level. 602 pts (321 male, 281 female; median age 34 years) with newly diagnosed, stages IA/IIA HL were registered into the RAPID trial between October 2003 and August 2010. Following 3 cycles ABVD, 571 pts had a PET scan of which 426 (74.6%) were classified as PET negative (score 1, n=301; score 2, n=125). 420 PET negative pts were randomised to receive IFRT (n=209) or NFT (n=211); 6 PET negative pts were not randomised (pt choice, n=3, clinician choice, n=2; error, n=1). 22 of 209 pts randomised to receive IFRT did not receive this treatment because 16 pts (PET score 1, n=14; PET score 2, n=2) declined after they became aware of the randomisation decision, 5 had died and 1 developed pneumocystis jiroveci pneumonia. After a median follow-up of 45.7 months from randomisation, 384 of 420 (91.4%) PET negative pts are alive and progression-free, 29 (6.9%) are alive and have progressed and 7 (1.7%) have died giving a combined 3-year PFS of 92.2% and overall survival (OS) of 98.3% in the randomised population. In the IFRT arm of the randomised PET negative population, 194 pts are alive and progression-free, 9 have progressed, and 6 have died (pneumonitis, n=2; HL, n=1; cardiovascular disease, n=1; intracerebal haemorrhage, n=1; angioimmunoblastic T cell lymphoma, n=1). In the NFT arm 190 pts are alive and progression-free, 20 have progressed, and 1 has died (bronchopneumonia, n=1). 3-year PFS is 93.8% IFRT versus 90.7% NFT (risk difference −2.9%, 95% CI −10.7 to 1.4%; the lower limit marginally exceeds the maximum allowable difference of −7%) and 3-year OS is 97.0% IFRT versus 99.5% NFT. For the 145 PET positive pts who received a 4thcycle ABVD and IFRT, 126 are alive and progression-free, 11 progressed, and 8 died to give a 3-year PFS of 85.9% and OS of 93.9% from registration. These results are summarized in the Table. These results show that in early stage HL, pts with a negative PET after 3 cycles of ABVD have an excellent prognosis without any further treatment. The 3-year PFS is slightly higher in the PET negative pts receiving IFRT (93.8% vs 90.7%), where a non-inferiority margin of 7% was deemed acceptable. We conclude that in stages IA/IIA HL, RT is unnecessary in the 75% of pts who become PET negative after 3 cycles ABVD. Such a response adapted approach based on centrally reviewed PET imaging reduces treatment time and costs, improves tolerability and most importantly removes the burden of early and late toxicity of radiotherapy from the PET negative population. Outcomes by PET status after 3 cycle ABVD and subsequent treatment Disclosures: No relevant conflicts of interest to declare.

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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