Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress
Clinical Collections
Advances in Alzheimer’s

At a glance: The ONWARDS insulin icodec trials

A round-up of the ONWARDS phase 3 clinical trials evaluating the novel weekly insulin icodec in people with diabetes.
ADVANCED SEARCH
Log in
Top
Radiation Oncology
Published in: Radiation Oncology 1/2019

Open Access 01-12-2019 | Lymphoma | Research

Comparative photon and proton dosimetry for patients with mediastinal lymphoma in the era of Monte Carlo treatment planning and variable relative biological effectiveness

Authors: Yolanda D. Tseng, Shadonna M. Maes, Gregory Kicska, Patricia Sponsellor, Erik Traneus, Tony Wong, Robert D. Stewart, Jatinder Saini

Published in: Radiation Oncology | Issue 1/2019

Login to get access

Abstract

Background

Existing pencil beam analytical (PBA) algorithms for proton therapy treatment planning are not ideal for sites with heterogeneous tissue density and do not account for the spatial variations in proton relative biological effectiveness (vRBE). Using a commercially available Monte Carlo (MC) treatment planning system, we compared various dosimetric endpoints between proton PBA, proton MC, and photon treatment plans among patients with mediastinal lymphoma.

Methods

Eight mediastinal lymphoma patients with both free breathing (FB) and deep inspiration breath hold (DIBH) CT simulation scans were analyzed. The original PBA plans were re-calculated with MC. New proton plans that used MC for both optimization and dose calculation with equivalent CTV/ITV coverage were also created. A vRBE model, which uses a published model for DNA double strand break (DSB) induction, was applied on MC plans to study the potential impact of vRBE on cardiac doses. Comparative photon plans were generated on the DIBH scan.

Results

Re-calculation of FB PBA plans with MC demonstrated significant under coverage of the ITV V99 and V95. Target coverage was recovered by re-optimizing the PT plan with MC with minimal change to OAR doses. Compared to photons with DIBH, MC-optimized FB and DIBH proton plans had significantly lower dose to the mean lung, lung V5, breast tissue, and spinal cord for similar target coverage. Even with application of vRBE in the proton plans, the putative increase in RBE at the end of range did not decrease the dosimetric advantages of proton therapy in cardiac substructures.

Conclusions

MC should be used for PT treatment planning of mediastinal lymphoma to ensure adequate coverage of target volumes. Our preliminary data suggests that MC-optimized PT plans have better sparing of the lung and breast tissue compared to photons. Also, the potential for end of range RBE effects are unlikely to be large enough to offset the dosimetric advantages of proton therapy in cardiac substructures for mediastinal targets, although these dosimetric findings require validation with late toxicity data.
Appendix
Available only for authorised users
Literature
1.
Hancock SL, Tucker MA, Hoppe RT. Factors affecting late mortality from heart disease after treatment of Hodgkin's disease. JAMA. 1993;270:1949–55.PubMedCrossRef
2.
Aleman BMP, van den Belt-Dusebout AW, Klokman WJ, van’t Veer MB, Bartelink H, van Leeuwen FE. Long-term cause-specific mortality of patients treated for Hodgkin’s disease. J Clin Oncol. 2003;21:3431–9.PubMedCrossRef
3.
van Nimwegen FA, Schaapveld M, Janus CM, Krol ADG, Petersen EJ, Raemaekers JM, Kok WEM, Aleman BMP, van Leeuwen FE. Cardiovascular disease after hodgkin lymphoma treatment: 40-year disease risk. JAMA Intern Med. 2015;175:1007–17.PubMedCrossRef
4.
De Bruin ML, Dorresteijn LDA, van't Veer MB, Krol ADG, van der Pal HJ, Kappelle AC, Boogerd W, Aleman BMP, van Leeuwen FE. Increased risk of stroke and transient ischemic attack in 5-year survivors of Hodgkin lymphoma. J National Cancer Institute. 2009;101:928–37.
5.
Travis LB, Hill DA, Dores GM, Gospodarowicz M, van Leeuwen FE, Holowaty E, Glimelius B, Andersson M, Wiklund T, Lynch CF, Van't Veer MB, Glimelius I, Storm H, Pukkala E, Stovall M, Curtis R, Boice JD, Gilbert E. Breast cancer following radiotherapy and chemotherapy among young women with hodgkin disease. JAMA. 2003;290:465–75.PubMedCrossRef
6.
Travis LB, Gospodarowicz M, Curtis RE, Aileen Clarke E, Andersson M, Glimelius B, Joensuu T, Lynch CF, van Leeuwen FE, Holowaty E, Storm H, Glimelius I, Pukkala E, Stovall M, Fraumeni JF, Boice JD, Gilbert E. Lung Cancer following chemotherapy and radiotherapy for Hodgkin's disease. J National Cancer Institute. 2002;94:182–92.
7.
Voong KR, McSpadden K, Pinnix CC, Shihadeh F, Reed V, Salehpour MR, Arzu I, Wang H, Hodgson D, Garcia J, Aristophanous M, Dabaja BS. 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.PubMedCrossRefPubMedCentral
8.
Paumier A, Ghalibafian M, Gilmore J, Beaudre A, Blanchard P, el Nemr M, Azoury F, al Hamokles H, Lefkopoulos D, Girinsky T. Dosimetric Benefits of Intensity-Modulated Radiotherapy Combined With the Deep-Inspiration Breath-Hold Technique in Patients With Mediastinal Hodgkin's Lymphoma. Int J Radiat Oncol*Biol*Phys. 2012;82:1522–7.CrossRefPubMed
9.
Hoppe BS, Flampouri S, Zaiden R, Slayton W, Sandler E, Ozdemir S, Dang NH, Lynch JW, Li Z, Morris CG, Mendenhall NP. Involved-Node Proton Therapy in Combined Modality Therapy for Hodgkin Lymphoma: Results of a Phase 2 Study. Int J Radiat Oncol*Biol*Phys. 2014;89:1053–9.CrossRefPubMed
10.
Taylor PA, Kry SF, Followill DS. Pencil Beam Algorithms Are Unsuitable for Proton Dose Calculations in Lung. Int J Radiat Oncol*Biol*Phys. 2017;99:750–6.PubMedPubMedCentralCrossRef
11.
Maes D, Saini J, Zeng J, Rengan R, Wong T, Bowen SR. Advanced proton beam dosimetry part II: Monte Carlo vs . pencil beam-based planning for lung cancer. Translational Lung Cancer Research; Vol 7, No 2 (April 2018): Translational Lung Cancer Research (Proton Therapy in Non-small cell lung cancer) 2018.
12.
Paganetti H, Niemierko A, Ancukiewicz M, Gerweck LE, Goitein M, Loeffler JS, Suit HD. Relative biological effectiveness (RBE) values for proton beam therapy. Int J Radiat Oncol*Biol*Phys. 2002;53:407–21.CrossRefPubMed
13.
Paganetti H. Relative biological effectiveness (RBE) values for proton beam therapy. Variations as a function of biological endpoint, dose, and linear energy transfer. Phys Med Biol. 2014;21:R419–72.CrossRef
14.
Tseng YD, Cutter DJ, Plastaras JP, Parikh RR, Cahlon O, Chuong MD, Dedeckova K, Khan MK, Lin S, McGee LA, Shen EY, Terezakis SA, Badiyan SN, Kirova YM, Hoppe RT, Mendenhall NP, Pankuch M, Flampouri S, Ricardi U, Hoppe BS. 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;99:825–42.CrossRefPubMed
15.
Rechner LA, Maraldo MV, Vogelius IR, Zhu XR, Dabaja BS, Brodin NP, Petersen PM, Specht L, Aznar MC. 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;125:41–7.PubMedPubMedCentralCrossRef
16.
Specht L, Yahalom J, Illidge T, Berthelsen AK, Constine LS, Eich HT, Girinsky T, Hoppe RT, Mauch P, Mikhaeel NG, Ng A. Modern Radiation Therapy for Hodgkin Lymphoma: Field and Dose Guidelines From the International Lymphoma Radiation Oncology Group (ILROG). Int J Radiat Oncol*Biol*Phys. 2014;89:854–62.CrossRefPubMed
17.
Girinsky T, van der Maazen R, Specht L, Aleman B, Poortmans P, Lievens Y, Meijnders P, Ghalibafian M, Meerwaldt J, Noordijk E. Involved-node radiotherapy (INRT) in patients with early Hodgkin lymphoma: concepts and guidelines. Radiother Oncol. 2006;79:270–7.PubMedCrossRef
18.
Feng M, Moran JM, Koelling T, Chughtai A, Chan JL, Freedman L, Hayman JA, Jagsi R, Jolly S, Larouere J, Soriano J, Marsh R, Pierce LJ. 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;79:10–8.CrossRefPubMed
19.
Saini J, Cao N, Bowen SR, Herrera M, Nicewonger D, Wong T, Bloch CD. Clinical commissioning of a pencil beam scanning treatment planning system for proton therapy. Int J Part Ther. 2016;3:51–60.PubMedPubMedCentralCrossRef
20.
Grassberger C, Dowdell S, Sharp G, Paganetti H. Motion mitigation for lung cancer patients treated with active scanning proton therapy. Med Phys. 2015;42:2462–9.PubMedPubMedCentralCrossRef
21.
Alshaikhi J, Doolan PJ, D'Souza D, Holloway SM, Amos RA, Royle G. Impact of varying planning parameters on proton pencil beam scanning dose distributions in four commercial treatment planning systems. Med Phys. 2019;46:1150–62.PubMedCrossRef
22.
Saini J, Traneus E, Maes D, Regmi R, Bowen SR, Bloch C, Wong T. Advanced proton beam Dosimetry part I: review and performance evaluation of dose calculation algorithms. Transl lung cancer res. 2018;7:171–9.PubMedPubMedCentralCrossRef
23.
Schreuder AN, Bridges DS, Rigsby L, Blakey M, Janson M, Hedrick SG Wilkinson JB. Validation of the RayStation Monte Carlo dose calculation algorithm using realistic animal tissue phantoms. J Appl Clin Med Phys. 2019;20:160-71.PubMedPubMedCentralCrossRef
24.
Tommasino F, Fellin F, Lorentini S, Farace P. Impact of dose engine algorithm in pencil beam scanning proton therapy for breast cancer. Physica medica : PM : an international journal devoted to the applications of physics to medicine and biology. official j Italian Assoc Biomed Phys (AIFB). 2018;50:7–12.
25.
Sasidharan BK, Aljabab S, Saini J, Wong T, Laramore G, Liao J Parvathaneni U, Bowen SR. Clinical Monte Carlo versus pencil beam treatment planning in nasopharyngeal patients receiving IMPT. Int J Part Ther. 2019;5:32–40.PubMedPubMedCentralCrossRef
26.
Widesott L, Lorentini S, Fracchiolla F, Farace P, Schwarz M. Improvements in pencil beam scanning proton therapy dose calculation accuracy in brain tumor cases with a commercial Monte Carlo algorithm. Phys Med Biol. 2018;63:145016.PubMedCrossRef
27.
Saini J, Maes D, Egan A, Bowen SR, St James S, Janson M, Wong T, Bloch C. Dosimetric evaluation of a commercial proton spot scanning Monte-Carlo dose algorithm: comparisons against measurements and simulations. Phys Med Biol. 2017;62:7659–81.CrossRef
28.
29.
Hasenbalg F, Neuenschwander H, Mini R, Born EJ. Collapsed cone convolution and analytical anisotropic algorithm dose calculations compared to VMC++ Monte Carlo simulations in clinical cases. Phys Med Biol. 2007;52:3679–91.PubMedCrossRef
30.
Mzenda B, Mugabe KV, Sims R, Godwin G, Loria D. Modeling and dosimetric performance evaluation of the RayStation treatment planning system. J Appl Clinical Med Phys. 2014;15:29–46.CrossRef
31.
Stewart RD, Yu VK, Georgakilas AG, Koumenis C, Park JH, Carlson DJ. Effects of radiation quality and oxygen on clustered DNA lesions and cell death. Radiat Res. 2011;176:587–602.PubMedCrossRef
32.
Stewart RD, Streitmatter SW, Argento DC, Kirkby C, Goorley JT, Moffitt G, Jevremovic T, Sandison GA. Rapid MCNP simulation of DNA double strand break (DSB) relative biological effectiveness (RBE) for photons, neutrons, and light ions. Phys Med Biol. 2015;60:8249.PubMedCrossRef
33.
34.
Semenenko VA, Stewart RD. Fast Monte Carlo simulation of DNA damage formed by electrons and light ions. Phys Med Biol. 2006;51:1693–706.PubMedCrossRef
35.
Carlson DJ, Stewart RD, Semenenko VA, Sandison GA. Combined use of Monte Carlo DNA damage simulations and deterministic repair models to examine putative mechanisms of cell killing. Radiat Res. 2008;169:447–59.PubMedCrossRef
36.
Stewart RD, Carlson DJ, Butkus MP, Hawkins R, Friedrich T, Scholz M. A comparison of mechanism-inspired models for particle relative biological effectiveness (RBE). Med Phys. 2018;45:e925–e52.PubMedCrossRef
37.
Hong L, Goitein M, Bucciolini M, Comiskey R, Gottschalk B, Rosenthal S, Serago C, Urie M. A pencil beam algorithm for proton dose calculations. Phys Med Biol. 1996;41:1305–30.PubMedCrossRef
38.
Edvardsson A, Kügele M, Alkner S, Enmark M, Nilsson J, Kristensen I, Kjellen E, Engelholm S, Ceberg S. Comparative treatment planning study for mediastinal Hodgkin’s lymphoma: impact on normal tissue dose using deep inspiration breath hold proton and photon therapy. Acta Oncol. 2018:1–10.
39.
Hoppe BS, Mendenhall NP, Louis D, Li Z, Flampouri S. Comparing breath hold and free breathing during intensity-modulated radiation therapy and proton therapy in patients with Mediastinal Hodgkin lymphoma. Int J Part Ther. 2017;3:492–6.PubMedPubMedCentralCrossRef
40.
Baues C, Marnitz S, Engert A, Baus W, Jablonska K, Fogliata A, Vasquez-Torres A, Scorsetti M, Cozzi L. Proton versus photon deep inspiration breath hold technique in patients with hodgkin lymphoma and mediastinal radiation. Radiat Oncol. 2018;13:122.
41.
De Bruin ML, Sparidans J, van't Veer MB, Noordijk EM, Louwman MWJ, Zijlstra JM, van den Berg H, Russell NS, Broeks A, Baaijens MHA, Aleman BMP, van Leeuwen FE. Breast Cancer risk in female survivors of Hodgkin's lymphoma: lower risk after smaller radiation volumes. J Clin Oncol. 2009;27:4239–46.
42.
Maraldo MV, Giusti F, Vogelius IR, Lundemann M, van der Kaaij MAE, Ramadan S, Meulemans B, Henry-Amar M, Aleman BMP, Raemaekers J, Meijinders P, Moser EC, Kluin-Nelemans HC, Feugier P, Casasnovas O, Fortpied C, Specht L. Cardiovascular disease after treatment for Hodgkin's lymphoma: an analysis of nine collaborative EORTC-LYSA trials. Lancet Haematol. 2015;2:e492–502.PubMedCrossRef
43.
Aleman BMP, van den Belt-Dusebout AW, De Bruin ML, Van't Veer MB, Baaijens MHA, de Boer JP, Hart AAM, Klokman WJ, Kuenen MA, Ouwens GM, Bartelink H, van Leeuwen FE. Late cardiotoxicity after treatment for Hodgkin lymphoma. Blood. 2007;109:1878.PubMedCrossRef
44.
Sud A, Thomsen H, Sundquist K, Houlston RS, Hemminki K. Risk of second Cancer in Hodgkin lymphoma survivors and influence of family history. J Clin Oncol. 2017;35:1584–90.PubMedPubMedCentralCrossRef
45.
Krul IM, Opstal-van Winden AWJ, Aleman BMP, Janus CPM, van Eggermond AM, De Bruin ML, Hauptmann M, Krol ADG, Schaapveld M, Broeks A, Kooijman KR, Fase S, Lybeert ML, Zijlstra JM, van der Maazen RWM, Kesminiene A, Diallo I, de Vathaire F, Russell NS, van Leeuwen FE. Breast Cancer Risk After Radiation Therapy for Hodgkin Lymphoma: Influence of Gonadal Hormone Exposure. Int J Radiat Oncol*Biol*Phys. 2017;99:843–53.
46.
Everett A, Flampouri S, Louis D, McDonald AM, Mendenhall NP, Li Z, Hoppe BS. Comparison of Radiation Techniques in Lower Mediastinal Lymphoma. Int J Radiat Oncol • Biol • Phys. 2018;102:S190–S1.CrossRef
47.
Dabaja BS, Hoppe BS, Plastaras JP, Newhauser W, Rosolova K, Flampouri S, Mohan R, Mikhaeel NG, Kirova Y, Specht L, Yahalom J. Proton therapy for adults with mediastinal lymphomas: the International Lymphoma Radiation Oncology Group guidelines. Blood. 2018:132–1635.
48.
Krämer M, Scholz M. Treatment planning for heavy-ion radiotherapy: calculation and optimization of biologically effective dose. Phys Med Biol. 2000;45:3319–30.PubMedCrossRef
49.
Scholz M, Matsufuji N, Kanai T. Test of the local effect model using clinical data: tumour control probability for lung tumours after treatment with carbon ion beams. Radiat Prot Dosim. 2006;122:478–9.CrossRef
50.
Krämer M, Scholz M. Rapid calculation of biological effects in ion radiotherapy. Phys Med Biol. 2006;51:1959–70.PubMedCrossRef
51.
Kase Y, Kanai T, Matsufuji N, Furusawa Y, Elsässer T, Scholz M. Biophysical calculation of cell survival probabilities using amorphous track structure models for heavy-ion irradiation. Phys Med Biol. 2007;53:37–59.PubMedCrossRef
52.
Frese MC, Yu VK, Stewart RD, Carlson DJ. A Mechanism-Based Approach to Predict the Relative Biological Effectiveness of Protons and Carbon Ions in Radiation Therapy. Int J Radiat Oncol*Biol*Phys. 2012;83:442–50.PubMedCrossRef
53.
Cutter DJ, Schaapveld M, Darby SC, Hauptmann M, van Nimwegen FA, Krol ADG, et al. Risk for Valvular Heart Disease After Treatment for Hodgkin Lymphoma. JNCI: J National Cancer Inst. 2015;107:djv008–djv.CrossRef
54.
van Nimwegen FA, Ntentas G, Darby SC, Schaapveld M, Hauptmann M, Lugtenburg PJ, Janus CPM, Daniels L, van Leeuwen FE, Cutter DJ, Aleman BMP. Risk of heart failure in survivors of Hodgkin lymphoma: effects of cardiac exposure to radiation and anthracyclines. Blood. 2017;129:2257.PubMedPubMedCentralCrossRef
55.
Booz J, Braby L, Coyne J, Kliauga P, Lindborg L, Menzel HG, Parmentier N. Report 36. Journal of the International Commission on Radiation Units and Measurements. 1983;os19.
56.
Elsässer T, Weyrather WK, Friedrich T, Durante M, Iancu G, Krämer M, Kragl G, Brons S, Winter M, Weber KJ, Scholz M. Quantification of the Relative Biological Effectiveness for Ion Beam Radiotherapy: Direct Experimental Comparison of Proton and Carbon Ion Beams and a Novel Approach for Treatment Planning. Int J Radiat Oncol*Biol*Phys. 2010;78:1177–83.CrossRefPubMed
57.
Friedrich T, Scholz U, Elsässer T, Durante M, Scholz M. Calculation of the biological effects of ion beams based on the microscopic spatial damage distribution pattern. Int J Radiat Biol. 2012;88:103–7.PubMedCrossRef
58.
Hawkins R. A microdosimetric-kinetic model of cell death from exposure to ionizing radiation of any LET, with experimental and clinical applications. Int J Radiat Biol. 1996;69:739–55.PubMedCrossRef
59.
Hawkins RB. A statistical theory of cell killing by radiation of varying linear energy transfer. Radiat Res. 1994;140:366–74.PubMedCrossRef
60.
Hawkins RB. A Microdosimetric-kinetic model for the effect of non-Poisson distribution of lethal lesions on the variation of RBE with LET. Radiat Res. 2003;160:61–9.PubMedCrossRef
61.
Hawkins RB. A microdosimetric-kinetic theory of the dependence of the RBE for cell death on LET. Med Phys. 1998;25:1157–70.PubMedCrossRef
62.
Wedenberg M, Lind BK, Hårdemark B. A model for the relative biological effectiveness of protons: the tissue specific parameter α/β of photons is a predictor for the sensitivity to LET changes. Acta Oncol. 2013;52:580–8.PubMedCrossRef
63.
McNamara A, Schuemann J, Paganetti H. A phenomenological relative biological effectiveness (RBE) model for proton therapy based on all published in vitro cell survival data. Phys Med Biol. 2015;60:8399–416.PubMedPubMedCentralCrossRef
64.
Friedland W, Schmitt E, Kundrát P, Dingfelder M, Baiocco G, Barbieri S, Ottolenghi A. Comprehensive track-structure based evaluation of DNA damage by light ions from radiotherapy-relevant energies down to stopping. Sci Rep. 2017;7:45161.
Metadata
Title
Comparative photon and proton dosimetry for patients with mediastinal lymphoma in the era of Monte Carlo treatment planning and variable relative biological effectiveness
Authors
Yolanda D. Tseng
Shadonna M. Maes
Gregory Kicska
Patricia Sponsellor
Erik Traneus
Tony Wong
Robert D. Stewart
Jatinder Saini
Publication date
01-12-2019
Publisher
BioMed Central
Keyword
Lymphoma
Published in
Radiation Oncology / Issue 1/2019
Electronic ISSN: 1748-717X
DOI
https://doi.org/10.1186/s13014-019-1432-8

Other articles of this Issue 1/2019

Radiation Oncology 1/2019 Go to the issue

Research

Albumin - bilirubin (ALBI) versus Child-Turcotte-Pugh (CTP) in prognosis of HCC after stereotactic body radiation therapy

Research

Adaptive radiotherapy for head and neck cancer reduces the requirement for rescans during treatment due to spinal cord dose

Research

Skeletal muscle mass correlates with increased toxicity during neoadjuvant radiochemotherapy in locally advanced esophageal cancer: A SAKK 75/08 substudy

Research

Altered lymphatic drainage patterns in re-operative sentinel lymph node biopsy for ipsilateral breast tumor recurrence

Research

Positive correlation between blood glucose and radiotherapy doses to the central gustatory system in Glioblastoma Multiforme patients

Research

In silico comparison of the dosimetric impacts of a greater omentum spacer for abdominal and pelvic tumors in carbon-ion, proton and photon radiotherapy