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High-dose hypofractionated pencil beam scanning carbon ion radiotherapy for lung tumors: Dosimetric impact of different spot sizes and robustness to interfractional uncertainties

      Highlights

      • Robust 4D optimization was investigated for carbon ion radiotherapy of lung tumors.
      • Two spot size libraries were compared for hypofractionated treatments.
      • Degradations caused by setup and motion uncertainties were evaluated in repeated 4DCTs.
      • Larger spots increased the lung dose but were highly robust to uncertainties.
      • Deep-seated tumors would benefit from larger spots in terms of plan robustness.

      Abstract

      Purpose

      The robustness against setup and motion uncertainties of gated four-dimensional restricted robust optimization (4DRRO) was investigated for hypofractionated carbon ion radiotherapy (CIRT) of lung tumors.

      Methods

      CIRT plans of 9 patients were optimized using 4DRRO strategy with 3 mm setup errors, 3% density errors and 3 breathing phases related to the gate window. The prescription was 60 Gy(RBE) in 4 fractions. Standard spots (SS) were compared to big spots (BS). Plans were recalculated on multiple 4DCTs acquired within 3 weeks from treatment simulation and rigidly registered with planning images using bone matching. Warped dose distributions were generated using deformable image registration and accumulated on the planning 4DCTs. Target coverage (D98%, D95% and V95%) and dose to lung were evaluated in the recalculated and accumulated dose distributions.

      Results

      Comparable target coverage was obtained with both spot sizes (p = 0.53 for D95%). The mean lung dose increased of 0.6 Gy(RBE) with BS (p = 0.0078), still respecting the dose constraint of a 4-fraction stereotactic treatment for the risk of radiation pneumonitis. Statistically significant differences were found in the recalculated and accumulated D95% (p = 0.048 and p = 0.024), with BS showing to be more robust. Using BS, the average degradations of the D98%, D95% and V95% in the accumulated doses were −2.7%, −1.6% and −1.5%.

      Conclusions

      Gated 4DRRO was highly robust against setup and motion uncertainties. BS increased the dose to healthy tissues but were more robust than SS. The selected optimization settings guaranteed adequate target coverage during the simulated treatment course with acceptable risk of toxicity.

      Keywords

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      References

      1. Particle Therapy Co-Operative Group (PTCOG), https://www.ptcog.ch.

        • Zhang X.
        • Li Y.
        • Pan X.
        • Xiaoqiang L.i.
        • Mohan R.
        • Komaki R.
        • et al.
        Intensity-modulated proton therapy reduces the dose to normal tissue compared with intensity-modulated radiation therapy or passive scattering proton therapy and enables individualized radical radiotherapy for extensive stage IIIB non-small-cell lung cancer: a virtual clinical study.
        Int J Radiat Oncol Biol Phys. 2010; 77: 357-366https://doi.org/10.1016/j.ijrobp.2009.04.028
        • Register S.P.
        • Zhang X.
        • Mohan R.
        • Chang J.Y.
        Proton stereotactic body radiation therapy for clinically challenging cases of centrally and superiorly located stage I non-small-cell lung cancer.
        Int J Radiat Oncol Biol Phys. 2011; 80: 1015-1022https://doi.org/10.1016/j.ijrobp.2010.03.012
        • Murray P.
        • Franks K.
        • Hanna G.G.
        A systematic review of outcomes following stereotactic ablative radiotherapy in the treatment of early-stage primary lung cancer.
        Br J Radiol. 2017; 90: 20160732https://doi.org/10.1259/bjr.20160732
        • Miyamoto T.
        • Baba M.
        • Sugane T.
        • Nakajima M.
        • Yashiro T.
        • Kagei K.
        • et al.
        Working Group for Lung Cancer. Carbon ion radiotherapy for stage I non-small cell lung cancer using a regimen of four fractions during 1 week.
        J Thorac Oncol. 2007; 2: 916-926https://doi.org/10.1097/JTO.0b013e3181560a68
        • Miyamoto T.
        • Baba M.
        • Yamamoto N.
        • Koto M.
        • Sugawara T.
        • Yashiro T.
        • et al.
        Working Group for Lung Cancer. Curative treatment of Stage I non-small-cell lung cancer with carbon ion beams using a hypofractionated regimen.
        Int J Radiat Oncol Biol Phys. 2007; 67: 750-758https://doi.org/10.1016/j.ijrobp.2006.10.006
        • Chi A.
        • Chen H.
        • Wen S.
        • Yan H.
        • Liao Z.
        Comparison of particle beam therapy and stereotactic body radiotherapy for early stage non-small cell lung cancer: a systematic review and hypothesis-generating meta-analysis.
        Radiother Oncol. 2017; 123: 346-354https://doi.org/10.1016/j.radonc.2017.05.007
        • Yamamoto N.
        • Miyamoto T.
        • Nakajima M.
        • Karube M.
        • Hayashi K.
        • Tsuji H.
        • et al.
        A Dose escalation clinical trial of single-fraction carbon ion radiotherapy for peripheral stage I non-small cell lung cancer.
        J Thorac Oncol. 2017; 12: 673-680https://doi.org/10.1016/j.jtho.2016.12.012
        • Hayashi K.
        • Yamamoto N.
        • Nakajima M.
        • Nomoto A.
        • Tsuji H.
        • Ogawa K.
        • et al.
        Clinical outcomes of carbon-ion radiotherapy for locally advanced non-small-cell lung cancer.
        Cancer Sci. 2019; 110: 734-741https://doi.org/10.1111/cas.2019.110.issue-210.1111/cas.13890
        • Chang J.Y.
        • Zhang X.
        • Knopf A.
        • Li H.
        • Mori S.
        • Dong L.
        • et al.
        Consensus guidelines for implementing pencil-beam scanning proton therapy for thoracic malignancies on behalf of the PTCOG thoracic and lymphoma subcommittee.
        Int J Radiat Oncol Biol Phys. 2017; 99: 41-50https://doi.org/10.1016/j.ijrobp.2017.05.014
        • Grassberger C.
        • Dowdell S.
        • Sharp G.
        • Paganetti H.
        Motion mitigation for lung cancer patients treated with active scanning proton therapy.
        Med Phys. 2015; 42: 2462-2469https://doi.org/10.1118/1.4916662
        • Liu W.
        • Schild S.E.
        • Chang J.Y.
        • Liao Z.
        • Chang Y.-H.
        • Wen Z.
        • et al.
        Exploratory study of 4D versus 3D robust optimization in intensity modulated proton therapy for lung cancer.
        Int J Radiat Oncol Biol Phys. 2016; 95: 523-533https://doi.org/10.1016/j.ijrobp.2015.11.002
        • Inoue T.
        • Widder J.
        • van Dijk L.V.
        • Takegawa H.
        • Koizumi M.
        • Takashina M.
        • et al.
        Limited impact of setup and range uncertainties, breathing motion, and interplay effects in robustly optimized intensity modulated proton therapy for stage III non-small cell lung cancer.
        Int J Radiat Oncol Biol Phys. 2016; 96: 661-669https://doi.org/10.1016/j.ijrobp.2016.06.2454
        • Engwall E.
        • Fredriksson A.
        • Glimelius L.
        4D robust optimization including uncertainties in time structures can reduce the interplay effect in proton pencil beam scanning radiation therapy.
        Med Phys. 2018; 45: 4020-4029https://doi.org/10.1002/mp.2018.45.issue-910.1002/mp.13094
        • Rossi S.
        The national centre for oncological hadrontherapy (CNAO): Status and perspectives.
        Phys Med. 2015; 31: 333-351https://doi.org/10.1016/j.ejmp.2015.03.001
        • Ciocca M.
        • Mirandola A.
        • Molinelli S.
        • Russo S.
        • Mastella E.
        • Vai A.
        • et al.
        Commissioning of the 4-D treatment delivery system for organ motion management in synchrotron-based scanning ion beams.
        Phys Med. 2016; 32: 1667-1671https://doi.org/10.1016/j.ejmp.2016.11.107
        • Mastella E.
        • Molinelli S.
        • Pella A.
        • Vai A.
        • Maestri D.
        • Vitolo V.
        • et al.
        4D strategies for lung tumors treated with hypofractionated scanning proton beam therapy: Dosimetric impact and robustness to interplay effects.
        Radiother Oncol. 2020; 146: 213-220https://doi.org/10.1016/j.radonc.2020.02.025
        • Clark K.
        • Vendt B.
        • Smith K.
        • Freymann J.
        • Kirby J.
        • Koppel P.
        • et al.
        The Cancer Imaging Archive (TCIA): maintaining and operating a public information repository.
        J Digit Imaging. 2013; 26: 1045-1057https://doi.org/10.1007/s10278-013-9622-7
        • Hugo G.D.
        • Weiss E.
        • Sleeman W.C.
        • Balik S.
        • Keall P.J.
        • Lu J.
        • et al.
        A longitudinal four-dimensional computed tomography and cone beam computed tomography dataset for image-guided radiation therapy research in lung cancer.
        Med Phys. 2017; 44: 762-771https://doi.org/10.1002/mp.12059
        • Timmerman R.
        • Paulus R.
        • Galvin J.
        • Michalski J.
        • Straube W.
        • Bradley J.
        • et al.
        Stereotactic body radiation therapy for inoperable early stage lung cancer.
        JAMA. 2010; 303: 1070-1076https://doi.org/10.1001/jama.2010.261
        • Mirandola A.
        • Molinelli S.
        • Vilches Freixas G.
        • Mairani A.
        • Gallio E.
        • Panizza D.
        • et al.
        Dosimetric commissioning and quality assurance of scanned ion beams at the Italian National Center for Oncological Hadrontherapy.
        Med Phys. 2015; 42: 5287-5300https://doi.org/10.1118/1.4928397
        • Krämer M.
        • Scholz M.
        Treatment planning for heavy-ion radiotherapy: calculation and optimization of biologically effective dose.
        Phys Med Biol. 2000; 45: 3319-3330https://doi.org/10.1088/0031-9155/45/11/314
        • Weistrand O.
        • Svensson S.
        The ANACONDA algorithm for deformable image registration in radiotherapy.
        Med Phys. 2015; 42: 40-53https://doi.org/10.1118/1.4894702
        • Nenoff L.
        • Ribeiro C.O.
        • Matter M.
        • Hafner L.
        • Josipovic M.
        • Langendijk J.A.
        • et al.
        Deformable image registration uncertainty for inter-fractional dose accumulation of lung cancer proton therapy.
        Radiother Oncol. 2020; 147: 178-185https://doi.org/10.1016/j.radonc.2020.04.046
        • Samavati N.
        • Velec M.
        • Brock K.
        A hybrid biomechanical intensity based deformable image registration of lung 4DCT.
        Phys Med Biol. 2015; 60: 3359-3373https://doi.org/10.1088/0031-9155/60/8/3359
        • Velec M.
        • Moseley J.L.
        • Svensson S.
        • Hårdemark B.
        • Jaffray D.A.
        • Brock K.K.
        Validation of biomechanical deformable image registration in the abdomen, thorax, and pelvis in a commercial radiotherapy treatment planning system.
        Med Phys. 2017; 44: 3407-3417https://doi.org/10.1002/mp.2017.44.issue-710.1002/mp.12307
        • Kadoya N.
        • Nakajima Y.
        • Saito M.
        • Miyabe Y.
        • Kurooka M.
        • Kito S.
        • et al.
        Multi-institutional validation study of commercially available deformable image registration software for thoracic images.
        Int J Radiat Oncol Biol Phys. 2016; 96: 422-431https://doi.org/10.1016/j.ijrobp.2016.05.012
        • Zhang L.
        • Wang Z.
        • Shi C.
        • Long T.
        • Xu X.G.
        The impact of robustness of deformable image registration on contour propagation and dose accumulation for head and neck adaptive radiotherapy.
        J Appl Clin Med Phys. 2018; 19: 185-194https://doi.org/10.1002/acm2.2018.19.issue-410.1002/acm2.12361
        • van de Water S.
        • van Dam I.
        • Schaart D.R.
        • Al-Mamgani A.
        • Heijmen B.J.M.
        • Hoogeman M.S.
        The price of robustness; impact of worst-case optimization on organ-at-risk dose and complication probability in intensity-modulated proton therapy for oropharyngeal cancer patients.
        Radiother Oncol. 2016; 120: 56-62https://doi.org/10.1016/j.radonc.2016.04.038
        • Flatten V.
        • Baumann K.S.
        • Weber U.
        • Engenhart-Cabillic R.
        • Zink K.
        Quantification of the dependencies of the Bragg peak degradation due to lung tissue in proton therapy on a CT-based lung tumor phantom.
        Phys Med Biol. 2019; 64155005https://doi.org/10.1088/1361-6560/ab2611
        • Choi K.
        • Mein S.
        • Kopp B.
        • Magro G.
        • Molinelli S.
        • Ciocca M.
        • et al.
        FRoG-a new calculation engine for clinical investigations with proton and carbon ion beams at CNAO.
        Cancers (Basel). 2018; 10: 395https://doi.org/10.3390/cancers10110395
        • Mein S.
        • Choi K.
        • Kopp B.
        • Tessonnier T.
        • Bauer J.
        • Ferrari A.
        • et al.
        Fast robust dose calculation on GPU for high-precision 1H, 4He, 12C and 16O ion therapy: the FRoG platform.
        Sci Rep. 2018; 8https://doi.org/10.1038/s41598-018-33194-4
        • Grassberger C.
        • Dowdell S.
        • Lomax A.
        • Sharp G.
        • Shackleford J.
        • Choi N.
        • et al.
        Motion interplay as a function of patient parameters and spot size in spot scanning proton therapy for lung cancer.
        Int J Radiat Oncol Biol Phys. 2013; 86: 380-386https://doi.org/10.1016/j.ijrobp.2013.01.024
        • Pollom E.L.
        • Chin A.L.
        • Diehn M.
        • Loo B.W.
        • Chang D.T.
        Normal tissue constraints for abdominal and thoracic stereotactic body radiotherapy.
        Semin Radiat Oncol. 2017; 27: 197-208https://doi.org/10.1016/j.semradonc.2017.02.001
        • Chang J.Y.
        • Li Q.-Q.
        • Xu Q.-Y.
        • Allen P.K.
        • Rebueno N.
        • Gomez D.R.
        • et al.
        Stereotactic ablative radiation therapy for centrally located early stage or isolated parenchymal recurrences of non-small cell lung cancer: how to fly in a “no fly zone”.
        Int J Radiat Oncol Biol Phys. 2014; 88: 1120-1128https://doi.org/10.1016/j.ijrobp.2014.01.022
        • Onishi H.
        • Araki T.
        • Shirato H.
        • Nagata Y.
        • Hiraoka M.
        • Gomi K.
        • et al.
        Stereotactic hypofractionated high-dose irradiation for stage I nonsmall cell lung carcinoma: clinical outcomes in 245 subjects in a Japanese multiinstitutional study.
        Cancer. 2004; 101: 1623-1631https://doi.org/10.1002/cncr.20539
        • Koshy M.
        • Malik R.
        • Weichselbaum R.R.
        • Sher D.J.
        Increasing radiation therapy dose is associated with improved survival in patients undergoing stereotactic body radiation therapy for stage I non-small-cell lung cancer.
        Int J Radiat Oncol Biol Phys. 2015; 91: 344-350https://doi.org/10.1016/j.ijrobp.2014.10.002
        • Li Y.
        • Kubota Y.
        • Kubo N.
        • Mizukami T.
        • Sakai M.
        • Kawamura H.
        • et al.
        Dose assessment for patients with stage I non-small cell lung cancer receiving passive scattering carbon-ion radiotherapy using daily computed tomographic images: a prospective study.
        Radiother Oncol. 2020; 144: 224-230https://doi.org/10.1016/j.radonc.2020.01.003
        • Fossati P.
        • Molinelli S.
        • Matsufuji N.
        • Ciocca M.
        • Mirandola A.
        • Mairani A.
        • et al.
        Dose prescription in carbon ion radiotherapy: a planning study to compare NIRS and LEM approaches with a clinically-oriented strategy.
        Phys Med Biol. 2012; 57: 7543-7554https://doi.org/10.1088/0031-9155/57/22/7543
        • Yu Z.H.
        • Lin S.H.
        • Balter P.
        • Zhang L.
        • Dong L.
        A comparison of tumor motion characteristics between early stage and locally advanced stage lung cancers.
        Radiother Oncol. 2012; 104: 33-38https://doi.org/10.1016/j.radonc.2012.04.010
        • Fattori G.
        • Riboldi M.
        • Pella A.
        • Peroni M.
        • Cerveri P.
        • Desplanques M.
        • et al.
        Image guided particle therapy in CNAO room 2: implementation and clinical validation.
        Phys Med. 2015; 31: 9-15https://doi.org/10.1016/j.ejmp.2014.10.075
        • Ricotti R.
        • Pella A.
        • Tagaste B.
        • Elisei G.
        • Fontana G.
        • Bonora M.
        • et al.
        Long-time clinical experience in patient setup for several particle therapy clinical indications: management of patient positioning and evaluation of setup reproducibility and stability.
        Br J Radiol. 2020; 93: 20190595https://doi.org/10.1259/bjr.20190595
        • Graeff C.
        Robustness of 4D-optimized scanned carbon ion beam therapy against interfractional changes in lung cancer.
        Radiother Oncol. 2017; 122: 387-392https://doi.org/10.1016/j.radonc.2016.12.017
        • Meschini G.
        • Vai A.
        • Paganelli C.
        • Molinelli S.
        • Fontana G.
        • Pella A.
        • et al.
        Virtual 4DCT from 4DMRI for the management of respiratory motion in carbon ion therapy of abdominal tumors.
        Med Phys. 2020; 47: 909-916https://doi.org/10.1002/mp.v47.310.1002/mp.13992
        • Kalantzopoulos C.
        • Meschini G.
        • Paganelli C.
        • Fontana G.
        • Vai A.
        • Preda L.
        • et al.
        Organ motion quantification and margins evaluation in carbon ion therapy of abdominal lesions.
        Phys Med. 2020; 75: 33-39https://doi.org/10.1016/j.ejmp.2020.05.014