The need for individualized studies to compare radiogenic second cancer (RSC) risk in proton versus photon Hodgkin Lymphoma patient treatments

Kenneth Homann, Rebecca Howell, John Eley, Dragan Mirkovic, Carol Etzel, Annelise Giebeler, Anita Mahajan, Rui Zhang, Wayne Newhauser

Abstract


For Hodgkin Lymphoma (HL), proton therapy has been shown to potentially reduce therapeutic dose to healthy tissue and therefore the risk of developing a radiogenic second cancer (RSC) relative to photon therapy. Currently, commercial treatment planning systems (TPS) do not account for stray radiation doses for these treatments and their risks of late effects.   Treatment plans were created and therapeutic doses were calculated with commercial TPSs for the breast, lung, and thyroid of nine HL patients. Stray dose contributions were added by thermoluminescent dosimeter (TLD) measurements in an anthropomorphic phantom for the intensity modulated radiation therapy (IMRT) treatments and personalized Monte Carlo simulations for the proton treatments. The mean relative risk (RR) of developing a RSC following HL treatment with proton therapies was then calculated and compared to photon IMRT, and reported with the metric ratio of relative risk (RRR). Results showed generally lower RSC risks after proton therapy than photon IMRT when averaged over all patients in the cohort for the breast (RRR = 0.84±0.03), lung (RRR  = 0.77±0.03), and thyroid (RRR = 0.83±0.05), but were not universal across all patients examined. Our findings revealed that it is important to include stray dose contributions when comparing the RSC risks for different HL treatment techniques and demonstrated the importance of personalized dose and risk calculations for modern HL radiotherapy.

Keywords


Hodgkin Lymphoma, In-Silico Clinical Trial, Proton Therapy, Photon Therapy, Radiation Risks, Monte Carlo Simulations, Measurements

Full Text:

PDF

References


Ward E, DeSantis C, Robbins A, et al. Childhood and adolescent cancer statistics, 2014. CA: A Cancer Journal for Clinicians. 2014;64:83-103.

Bleyer A, Viny A, Barr R. Cancer in 15- to 29-year-olds by primary site. Oncologist. 2006;11:590-601.

Constine LS, Tarbell N, Hudson MM, et al. Subsequent malignancies in children treated for Hodgkin's disease: associations with gender and radiation dose. Int J Radiat Oncol Biol Phys. 2008;72(1):24-33.

Bhatia S, Yasui Y, Robison LL, et al. High risk of subsequent neoplasms continues with extended follow-up of childhood Hodgkin's disease: report from the Late Effects Study Group. J Clin Oncol. 2003;21(23):4386-94.

Castellino SM, Geiger AM, Mertens AC, et al. Morbidity and mortality in long-term survivors of Hodgkin lymphoma: a report from the Childhood Cancer Survivor Study. Blood. 2011;117(6):1806-16.

Ng AK, Bernardo MP, Weller E, et al. Long-term survival and competing causes of death in patients with early-stage Hodgkin's disease treated at age 50 or younger. J Clin Oncol. 2002;20(8):2101-8.

Aleman BM, van den Belt-Dusebout AW, Klokman WJ, et al. Long-term cause-specific mortality of patients treated for Hodgkin's disease. J Clin Oncol. 2003;21(18):3431-39.

Schneider U, Lomax A, Lombriser N. Comparative risk assessment of secondary cancer incidence after treatment of Hodgkin's disease with photon and proton radiation. Radiat Res. 2000; 154(4):382-88.

Chera BS, Rodriguez C, Morris CG, et al. Dosimetric comparison of three different involved nodal irradiation techniques for stage II Hodgkin's lymphoma patients: conventional radiotherapy, intensity-modulated radiotherapy, and three-dimensional proton radiotherapy. Int J Radiat Oncol Biol Phys. 2009;75(4):1173-80.

Andolino DL, Hoene T, Xiao L, et al. Dosimetric comparison of involved-field three-dimensional conformal photon radiotherapy and breast-sparing proton therapy for the treatment of Hodgkin's lymphoma in female pediatric patients Int J Radiat Oncol Biol Phys. 2011;81(4):e667-71.

Cella L, Conson M, Pressello MC, et al. Hodgkin's lymphoma emerging radiation treatment techniques: trade-offs between late radio-induced toxicities and secondary malignant neoplasms. Radiat Oncol. 2013;8(1):22.

Newhauser W, Jones T, Swerdloff S, et al. Anonymization of DICOM electronic medical records for radiation therapy. Comput Biol Med. 2014;53:134-40.

Wambersie A, Jones DTL, Suit HD. Presentation of the ICRU-IAEA joint report "Prescribing, Recording, and Reporting Proton-beam Therapy". Strahlenther Onkol. 2007;183:87-9.

Howell RM, Scarboro SB, Kry SF, Yaldo DZ. Accuracy of out-of-field dose calculations by a commercial treatment planning system. Phys Med Biol. 2010;55(23):6999-7008.

Joosten A, Bochud F, Baechler S, et al. Variability of a peripheral dose among various linac geometries for second cancer risk assessment. Phys Med Biol. 2011;56(16):5131-51.

Howell RM, Scarboro SB, Taddei PJ, et al. Methodology for determining doses to in-field, out-of-field and partially in-field organs for late effects studies in photon radiotherapy. Phys Med Biol. 2010;55(23):7009-23.

Newhauser W, Fontenot J, Zheng Y, et al. A Monte-Carlo based dose engine for proton radiotherapy treatment planning. Med Phys. 2007;34(6):2406.

Schneider U, Agosteo S, Pedroni E, Besserer J. Secondary neutron dose during proton therapy using spot scanning. Int J Radiat Oncol Biol Phys. 2002;53(1):244-51.

Newhauser WD, Fontenot JD, Mahajan A, et al. The risk of developing a second cancer after receiving craniospinal proton irradiation. Phys Med Biol. 2009;54(8):2277-91.

Brenner DJ, Hall EJ. Secondary neutrons in clinical proton radiotherapy: a charged issue. Radiother Oncol. 2008;86(2):165-70.

National Research Council (U.S.). Committee to Assess Health Risks from Exposure to Low Level of Ionizing Radiation. Health risks from exposure to low levels of ionizing radiation : BEIR VII Phase 2. Washington, D.C.: National Academies Press; 2006.

Friedman DL, Whitton J, Leisenring W, et al. Subsequent neoplasms in 5-year survivors of childhood cancer: the Childhood Cancer Survivor Study. J Natl Cancer Inst. 2010;102(14):1083-95.

Zhang R, Mirkovic D, Newhauser WD. Visualization of risk of radiogenic second cancer in the organs and tissues of the human body. Radiat Oncol. 2015;10(1):107.

NCRP. Report No. 170 - Second Primary Cancers and Cardiovascualr Disease After Radiation Therapy. NCRP Publications; 2011:386.

Berrington de Gonzalez A, Gilbert E, Curtis R, et al. Second solid cancers after radiation therapy: a systematic review of the epidemiologic studies of the radiation dose-response relationship. Int J Radiat Oncol Biol Phys. 2013;86(2):224-33.

Kaplan S, Garrick BJ. On the quantitative definition of risk. Risk Analysis. 1981;1(1):11-27.

Rechner LA, Howell RM, Zhang R, et al. Risk of radiogenic second cancers following volumetric modulated arc therapy and proton arc therapy for prostate cancer. Phys Med Biol. 2012; 57(21):7117-32.

Fontenot JD, Lee AK, Newhauser WD. Risk of secondary malignant neoplasms from proton therapy and intensity-modulated x-ray therapy for early-stage prostate cancer. Int J Radiat Oncol Biol Phys. 2009;74(2):616-22.

Taddei PJ, Mahajan A, Mirkovic D, et al. Predicted risks of second malignant neoplasm incidence and mortality due to secondary neutrons in a girl and boy receiving proton craniospinal irradiation. Phys Med Biol. 2010;55(23):7067-80.

Taddei PJ, Howell RM, Krishnan S, et al. Risk of second malignant neoplasm following proton versus intensity-modulated photon radiotherapies for hepatocellular carcinoma. Phys Med Biol. 2010;55(23):7055-65.

Paganetti H, Athar BS, Moteabbed M, et al. Assessment of radiation-induced second cancer risks in proton therapy and IMRT for organs inside the primary radiation field. Phys Med Biol. 2012;57(19):6047-61.

De Bruin ML, Sparidans J, van't Veer MB, et al. Breast cancer risk in female survivors of Hodgkin's lymphoma: lower risk after smaller radiation volumes. J Clin Oncol. 2009; 27(26):4239-46.

Ng AK, Kenney LB, Gilbert ES, et al. Secondary malignancies across the age spectrum. Semin Radiat Oncol. 2010;20(1):67-78.

Weber DC, Johanson S, Peguret N, et al. Predicted risk of radiation-induced cancers after involved field and involved node radiotherapy with or without intensity modulation for early-stage hodgkin lymphoma in female patients. Int J Radiat Oncol Biol Phys. 2011;81(2):490-7.

Zheng Y, Fontenot J, Taddei P, et al. Monte Carlo simulations of neutron spectral fluence, radiation weighting factor and ambient dose equivalent for a passively scattered proton therapy unit. Phys Med Biol. 2008;53(1):187-201.

Little MP. Comparison of the risks of cancer incidence and mortality following radiation therapy for benign and malignant disease with the cancer risks observed in the Japanese A-bomb survivors. Int J Radiat Biol. 2001;77(4):431-64.

Dores GM, Metayer C, Curtis RE, et al. Second malignant neoplasms among long-term survivors of Hodgkin's disease: a population-based evaluation over 25 years. J Clin Oncol. 2002; 20(16):3484-94.

Suit H, Goldberg S, Niemierko A, et al. Secondary carcinogenesis in patients treated with radiation: a review of data on radiation-induced cancers in human, non-human primate, canine and rodent subjects. Radiat Res. 2007;167(1):12-42.

Koh ES, Tran TH, Heydarian M, et al. A comparison of mantle versus involved-field radiotherapy for Hodgkin's lymphoma: reduction in normal tissue dose and second cancer risk. Radiat Oncol. 2007;2:13.

Girinsky T, van der Maazen R, Specht L, et al. Involved-node radiotherapy (INRT) in patients with early Hodgkin lymphoma: concepts and guidelines. Radiother Oncol. 2006;79(3):270-7.




DOI: http://dx.doi.org/10.14319/jpt.11.8

Copyright (c) 2016 Kenneth Homann

Creative Commons License
This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.

-------------------------------------------

© Journal of Proton Therapy (ISSN 2469-5491)

To make sure that you can receive messages from us, please add the 'protonjournal.org' and 'protonjournal.com' domains to your e-mail 'safe list'. If you do not receive e-mail in your 'inbox', please check your 'bulk mail' or 'junk mail' folders.