PURPOSE: Radiation therapy (RT) improves control of Hodgkin lymphoma (HL), but patients who undergo RT are at risk for late effects, including cardiovascular disease and second cancers, because of radiation doses to organs at risk (OARs). Proton therapy (PT) can reduce OAR doses compared with conventional photon RT. However, access to PT is currently limited, so referrals must be appropriately selective. We aimed to identify subgroups of patients with HL who could benefit the most dosimetrically from RT with PT based on the prechemotherapy disease characteristics. METHODS AND MATERIALS: Normal tissue radiation doses were calculated for 21 patients with HL who were treated with deep-inspiration breath-hold pencil-beam scanning (PBS) PT and compared with doses from 3-dimensional conformal (3D-CRT) and partial arc volumetric modulated (PartArc) photon RT. Prechemotherapy disease characteristics associated with significant dosimetric benefits from PBS compared with photon RT were identified. RESULTS: Treatment with PBS was well tolerated and provided with good local control. PBS provided dosimetric advantages for patients whose clinical treatment volume extended below the seventh thoracic level and for female patients with axillary disease. In addition, an increasing dosimetric benefit for some OARs was observed for increasing target volume. PBS significantly reduced the mean dose to the heart, breast, lungs, spinal cord, and esophagus. Dose homogeneity and conformity within the target volume were also superior with PBS, but some high-dose measures and hot spots were increased with PBS compared with partial arc volumetric modulated photon RT. CONCLUSIONS: PBS gives good target coverage and local control while providing reductions in radiation dose to OARs for individuals who receive RT for HL compared with advanced photon RT. Our findings highlight groups of patients who would be expected to gain more dosimetric benefit from PBS. These findings facilitate the selection of patients who should be considered a priority for PT.

CRUK MRC Oxford Institute for Radiation Oncology Department of Oncology University of Oxford Oxford United Kingdom

Nuffield Department of Population Health University of Oxford Oxford United Kingdom

Nuffield Department of Population Health University of Oxford Oxford United Kingdom; Manchester Cancer Research Centre Division of Cancer Sciences School of Medical Sciences Faculty of Biology Medicine and Health The University of Manchester Manchester United Kingdom

Nuffield Department of Population Health University of Oxford Oxford United Kingdom; Oxford Cancer Centre Oxford University Hospitals NHS Foundation Trust Oxford United Kingdom

Proton Therapy Center Czech s r o Prague Czech Republic

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Darby S.C., Ewertz M., McGale P. Risk of ischemic heart disease in women after radiotherapy for breast cancer. N Engl J Med. 2013;368:987–998. PubMed

van Nimwegen F.A., Schaapveld M., Cutter D.J. Radiation dose-response relationship for risk of coronary heart disease in survivors of Hodgkin lymphoma. J Clin Oncol. 2016;34:235–243. PubMed

van Nimwegen F.A., Ntentas G., Darby S.C. Risk of heart failure in survivors of Hodgkin lymphoma: Effects of cardiac exposure to radiation and anthracyclines. Blood. 2017;129:2257–2265. PubMed PMC

Maraldo M.V., Giusti F., Vogelius I.R. Cardiovascular disease after treatment for Hodgkin's lymphoma: An analysis of nine collaborative EORTC-LYSA trials. Lancet Haematol. 2015;2:e492–e502. PubMed

De Bruin M.L., Dorresteijn L.D., van't Veer M.B. Increased risk of stroke and transient ischemic attack in 5-year survivors of hodgkin lymphoma. J Natl Cancer Inst. 2009;101:928–937. PubMed

van Nimwegen F.A., Schaapveld M., Janus C.P. Cardiovascular disease after Hodgkin lymphoma treatment: 40-year disease risk. JAMA Intern Med. 2015;175:1007–1017. PubMed

Travis L.B., Hill D.A., Dores G.M. Breast cancer following radiotherapy and chemotherapy among young women with hodgkin disease. JAMA. 2003;290:465–475. PubMed

Morton L., Gilbert E., Stovall M. Risk of esophageal cancer following radiotherapy for Hodgkin lymphoma. Haematologica. 2014;99:e193–e196. PubMed PMC

Travis L.B., Gilbert E. Lung cancer after Hodgkin lymphoma: The roles of chemotherapy, radiotherapy and tobacco use. Radiat Res. 2005;163:695–696. PubMed

Van Leeuwen F.E., Klokman W.J., Hagenbeek A. Second cancer risk following Hodgkin's disease: a 20-year follow-up study. J Clin Oncol. 2014;12:312–325. PubMed

Tseng Y.D., Cutter D.J., Plastaras J.P. Evidence-based review on the use of proton therapy in lymphoma from the Particle Therapy Cooperative Group (PTCOG) lymphoma subcommittee. Int J Radiat Oncol Biol Phys. 2017;99:825–842. PubMed

Aznar M.C., Maraldo M.V., Schut D.A. Minimizing late effects for patients with mediastinal Hodgkin lymphoma: Deep inspiration breath-hold, IMRT, or both? Int J Radiat Oncol Biol Phys. 2015;92:169–174. PubMed

Fiandra C., Filippi A.R., Catuzzo P. Different IMRT solutions vs. 3D-conformal radiotherapy in early stage Hodgkin's lymphoma: Dosimetric comparison and clinical considerations. Radiat Oncol. 2012;7:186. PubMed PMC

Voong K.R., McSpadden K., Pinnix C.C. Dosimetric advantages of a ‘butterfly’ technique for intensity-modulated radiation therapy for young female patients with mediastinal Hodgkin's lymphoma. Radiat Oncol. 2014;9:94. PubMed PMC

Filippi A.R., Ragona R., Piva C. Optimized volumetric modulated arc therapy versus 3D-CRT for early stage mediastinal Hodgkin lymphoma without axillary involvement: A comparison of second cancers and heart disease risk. Int J Radiat Oncol Biol Phys. 2015;92:161–168. PubMed

Rechner L.A., Maraldo M.V., Vogelius I.R. Life years lost attributable to late effects after radiotherapy for early stage Hodgkin lymphoma: The impact of proton therapy and/or deep inspiration breath hold. Radiother Oncol. 2017;125:41–47. PubMed PMC

Langendijk J.A., Lambin P., De Ruysscher D., Widder J., Bos M., Verheij M. Selection of patients for radiotherapy with protons aiming at reduction of side effects: The model-based approach. Radiother Oncol. 2013;107:267–273. PubMed

Specht L., Yahalom J., Illidge T. Modern radiation therapy for Hodgkin lymphoma: Field and dose guidelines from the International Lymphoma Radiation Oncology Group (ILROG) Radiat Oncol Biol. 2014;89:854–862. PubMed

Feng M., Moran J.M., Koelling T. Development and validation of a heart atlas to study cardiac exposure to radiation following treatment for breast cancer. Int J Radiat Oncol Biol Phys. 2011;79:10–18. PubMed PMC

Shaw E., Kline R., Gillin M. Radiation therapy oncology group: Radiosurgery quality assurance guidelines. Int J Radiat Oncol. 1993;27:1231–1239. PubMed

Dabaja B.S., Hoppe B.S., Plastaras J.P. Proton therapy for adults with mediastinal lymphomas: The International Lymphoma Radiation Oncology Group (ILROG) guidelines. Blood. 2018;132:1635–1646. PubMed PMC

Hahn E., Jiang H., Ng A. Late cardiac toxicity after mediastinal radiotherapy for Hodgkin lymphoma: Contributions of coronary artery and whole heart dose-volume variables to risk prediction. J Radiat Oncol Biol Phys. 2017;98:1116–1123. PubMed

Cutter D.J., Schaapveld M., Darby S.C. Risk of valvular heart disease after treatment for Hodgkin lymphoma. J Natl Cancer Inst. 2015;107:djv008. PubMed PMC

Vykydal Z., Andrlík M., Bártová H., Králík M., Šolc J., Vondráček V. Measurement of secondary neutrons generated during proton therapy. Radiat Prot Dosimetry. 2016;172:341–345. PubMed

Cheson B.D., Fisher R.I., Barrington S.F. Recommendations for initial evaluation, staging, and response assessment of Hodgkin and non-Hodgkin lymphoma: The Lugano classification. J Clin Oncol. 2014;32:3059–3067. PubMed PMC

Proton Therapy in Supradiaphragmatic Lymphoma: Predicting Treatment-Related Mortality to Help Optimize Patient Selection