Dr. David J. Cutter1,2, Dr. Johanna Ramroth1, Patricia Diez3, Andy Buckle2, David Kennedy1, Bilyana Popova4, Laura Clifton-Hadley4, Prof Tim Illidge5, Prof Sarah C. Darby1, Prof John Radford5
1 Clinical Trial Service Unit, Nuffield Department of Population Health, University of Oxford, Richard Doll Building, Old Road Campus, Roosevelt Drive, Oxford, OX3 7LF, UK, 2 Oxford Cancer and Haematology Centre, Oxford University Hospitals NHS Trust, Churchill Hospital, Old Road, Oxford, OX3 7LE, UK, 3 National Radiotherapy Trials Quality Assurance Group, Mount Vernon Cancer Centre, Northwood, Middlesex, UK, 4 Cancer Research UK and UCL Cancer Trials Centre, London, UK, 5 University of Manchester, Manchester Cancer Research Centre, Manchester Academic Health Science Centre, The Christie NHS Foundation Trust, Manchester, UK
Context: A contemporary management decision in early stage Hodgkin lymphoma (ES-HL) involves balancing the risk of adverse effects if radiotherapy (RT) is given versus the increased risk of relapse if it is not. The RAPID trial studied the 3-year non-inferiority of omitting RT in patients with a complete metabolic response on positron-emission tomography (PET-ve) after 3 cycles of doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) chemotherapy. The present study estimates the possible reduction in 30-year cardiovascular risks from omitting RT in this cohort of patients.
Methods: Individualised cardiovascular dosimetry was performed for patients who received involved field radiotherapy (IFRT) within the RAPID trial. Cardiac and carotid radiation doses were combined with population-based rates to predict 30-year cardiovascular mortality and incidence.
Results: Dosimetry was completed for 247 of 312 patients who received IFRT in the trial, including 144 PET-ve patients. The average mean whole heart dose (MWHD) for PET-ve patients was 4.0 Gy. For 43% the MWHD was < 0.5 Gy, while for 10%, 17%, 15% and 15% it was in ranges 0.5 to <1, 1 to <5, 5 to <10 and ≥ 10 Gy respectively. The predicted 30-year absolute excess cardiac mortality for AVBD+IFRT compared to ABVD alone in these five dose categories was 0.39%, 0.46%, 0.75%, 1.41% and 2.67% (0.97% overall). The corresponding -predicted 30-year excess incidence of heart disease was 2.77%, 3.26%, 5.32%, 10.05% and 19.30% (9.95% overall, see figure). Extent of mediastinal involvement was the main determinant of cardiac dose and therefore of cardiac risk. ABVD alone was predicted to increase the risk of cardiac mortality by 0.59% and incidence by 4.5% due to anthracycline exposure. The predicted 30-year absolute excess stroke mortality for PET-ve patients who received IFRT was 0.19% and the 30-year excess incidence 3.1%.
Conclusion: Most PET–ve patients received a low cardiac dose from IFRT. The majority of patients (>70%) could receive the benefit of radiotherapy treatment without the cardiac risk from radiation exceeding that estimated from anthracycline exposure. For a smaller proportion, who received high cardiac radiation doses, omission of IFRT with an accepted increased relapse risk may be a better option. Accurate assessment of cardiovascular (and other, e.g. second cancer) risks at diagnosis will allow individualisation of the decision whether to omit RT or to consider advanced RT techniques in ES-HL.