Clinical Intensity Modulated Proton Therapy for Hodgkin Lymphoma: Which Patients Benefit the Most?

Ntentas, Georgios; Dědečková, K.; Andrlík, Michal; Aznar, Marianne C.; George, Ben; Kubeš, Jiří; Darby, Sarah C.

doi:10.1016/j.prro.2019.01.006

Cited by 30 publications

(42 citation statements)

References 24 publications

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“…The analysis of dosevolume metrics demonstrated a systematic incremental sparing of all OARs achievable with protons over photons. These results are in line with other planning evaluations [4][5][6]. Existing data from literature confirm the low toxicity profile expected from protons.…”

Section: Discussionsupporting

confidence: 90%

“…carcinogenesis). Simple methods based on the investigation of physical dose distributions or simple complication models, mostly at planning level, have been discussed but could only provide general indications and not individualized selection criteria [4][5][6][7][8]. The best approach to validation would be the execution of properly sized and defined clinical trials but this could be limited by ethical considerations, the time needed to obtain the results and the costs of execution.…”

Section: Introductionmentioning

confidence: 99%

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Intensity modulated proton therapy compared to volumetric modulated arc therapy in the irradiation of young female patients with hodgkin’s lymphoma. Assessment of risk of toxicity and secondary cancer induction

et al. 2020

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Background: To investigate the role of intensity modulated proton therapy (IMPT) compared to volumetric modulated arc therapy (VMAT) for advanced supradiaphragmatic Hodgkin's lymphoma (HL) in young female patients by assessing dosimetric features and modelling the risk of treatment related complications and radiationinduced secondary malignancies. Methods: A group of 20 cases (planned according to the involved-site approach) were retrospectively investigated in a comparative planning study. Intensity modulated proton plans (IMPT) were compared to VMAT RapidArc plans (RA). Estimates of toxicity were derived from normal tissue complication probability (NTCP) calculations with either the Lyman or the Poisson models for a number of endpoints. Estimates of the risk of secondary cancer induction were determined for lungs, breasts, esophagus and thyroid. A simple model-based selection strategy was considered as a feasibility proof for the individualized selection of patients suitable for proton therapy. Results: IMPT and VMAT plans resulted equivalent in terms of target dose distributions, both were capable to ensure high coverage and homogeneity. In terms of conformality, IMPT resulted~10% better than RA plans. Concerning organs at risk, IMPT data presented a systematic improvement (highly significant) over RA for all organs, particularly in the dose range up to 20Gy. This lead to a composite average reduction of NTCP of 2.90 ± 2.24 and a reduction of 0.26 ± 0.22 in the relative risk of cardiac failures. The excess absolute risk per 10,000 patients-years of secondary cancer induction was reduced, with IMPT, of 9.1 ± 3.2, 7.2 ± 3.7 for breast and lung compared to RA. The gain in EAR for thyroid and esophagus was lower than 1. Depending on the arbitrary thresholds applied, the selection rate for proton treatment would have ranged from 5 to 75%.

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Section: Discussionsupporting

confidence: 90%

Section: Introductionmentioning

confidence: 99%

Intensity modulated proton therapy compared to volumetric modulated arc therapy in the irradiation of young female patients with hodgkin’s lymphoma. Assessment of risk of toxicity and secondary cancer induction

et al. 2020

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“…2018 the ILROG published a guideline [72] in which they proposed advantages especially for proton RT for lower mediastinal involvement. Recently Everett et al [42] and Ntentas et al [43] published data dealing with that issue as well. In both studies doses to organs at risk, in particular to the heart, the lungs and the breast tissue is lower for proton RT compared to IMRT photon approaches in lower mediastinal disease.…”

Section: Discussionmentioning

confidence: 99%

“…4D-CT, internal target volume concepts, breath-hold techniques) and robustness optimized IMPT plans are therefore required. In the adult population particle therapy has been used in limited studies [40–43] but only few data [44] are available analyzing PT in pediatric or adolescent patients suffering from Hodgkin’s disease.…”

Section: Introductionmentioning

confidence: 99%

Advantage of proton-radiotherapy for pediatric patients and adolescents with Hodgkin’s disease

et al. 2019

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Radiotherapy is frequently used in the therapy of lymphoma. Since lymphoma, for example Hodgkin’s disease, frequently affect rather young patients, the induction of secondary cancer or other long-term adverse effects after irradiation are important issues to deal with. Especially for mediastinal manifestations numerous organs and substructures at risk play a role. The heart, its coronary vessels and cardiac valves, the lungs, the thyroid and, for female patients, the breast tissue are only the most important organs at risk. In this study we investigated if proton-radiotherapy might reduce the dose delivered to the organs at risk and thus minimize the therapy-associated toxicity. Methods In this work we compared the dose delivered to the heart, its coronary vessels and valves, the lungs, the thyroid gland and the breast tissue by different volumetric photon plans and a proton plan, all calculated for a dose of 28.8 Gy (EURO-NET-PHL-C2). Target Volumes have been defined by F18-FDG PET-positive areas, following a modified involved node approach. Data from ten young female patients with mediastinal lymphoma have been evaluated. Three different modern volumetric IMRT (VMAT) photon plans have been benchmarked against each other and against proton-irradiation concepts. For plan-evaluation conformity- and homogeneity-indices have been calculated as suggested in ICRU 83. The target volume coverage as well as the dose to important organs at risk as the heart with its substructures, the lungs, the breast tissue, the thyroid and the spinal cord were calculated and compared. For statistical evaluation mean doses to organs at risk were evaluated by non- parametric Kruskal-Wallis calculations with pairwise comparisons. Results Proton-plans and three different volumetric photon-plans have been calculated. Proton irradiation results in significant lower doses delivered to organ at risk. The median doses and the mean doses could be decreased while PTV coverage is comparable. As well conformity as homogeneity are slightly better for proton plans. For several organs a risk reduction for secondary malignancies has been calculated using literature data as reference. According to the used data derived from literature especially the secondary breast cancer risk, the secondary lung cancer risk and the risk for ischemic cardiac insults can be reduced significantly by using protons for radiotherapy of mediastinal lymphomas. Conclusion Irradiation with protons for mediastinal Hodgkin-lymphoma results in significant lower doses for almost all organs at risk and is suitable to reduce long term side effects for pediatric and adolescent patients. Electronic supplementary material The online version of this article (10.1186/s13014-019-1360-7) contains supplementary material, which is available to authorized users.

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“…Intensity-modulated proton therapy (IMPT) offers superior targeting with normal tissue sparing [ 30 , 31 ]. Pencil beam scanning proton therapy provides excellent coverage and local control while reducing dose to organs at risk (OARs) for patients with mediastinal HL [ 32 ]. Given the promising data with CSS optimization and the opening of our institution's proton therapy center in June 2015, we began to enroll patients that we intended to treat with IMPT.…”

Section: Introductionmentioning

confidence: 99%

Reducing Heart Dose with Protons and Cardiac Substructure Sparing for Mediastinal Lymphoma Treatment

Taparra

Lester

Harmsen

et al. 2020

International Journal of Particle Therapy

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Purpose Electrocardiogram-gated computed tomography with coronary angiography can be used for cardiac substructure sparing (CSS) optimization, which identifies and improves avoidance of cardiac substructures when treating with intensity modulated radiotherapy (IMRT). We investigated whether intensity modulated proton therapy (IMPT) would further reduce dose to cardiac substructures for patients with mediastinal lymphoma. Patients and Methods Twenty-one patients with mediastinal lymphoma were enrolled and underwent electrocardiogram-gated computed tomography angiography during or shortly after simulation for radiotherapy planning. Thirteen patients with delineated cardiac substructures underwent comparative planning with both IMPT and IMRT. Plans were normalized for equivalent (95%) target volume coverage for treatment comparison. Results Thirteen patients met criteria for this study. The median size of the mediastinal lymphadenopathy was 7.9 cm at the greatest diameter. Compared with IMRT-CSS, IMPT-CSS significantly reduced mean dose to all cardiac substructures, including 3 coronary arteries and 4 cardiac valves. Use of IMPT significantly reduced average whole-heart dose from 9.6 to 4.9 Gy (P < .0001), and average mean lung dose was 9.7 vs 5.8 Gy (P < .0001). Prospectively defined clinically meaningful improvement was observed in at least 1 coronary artery in 9 patients (69%), at least 1 cardiac valve in 10 patients (77%), and whole heart in all 13 patients. Conclusions For patients with mediastinal lymphoma, IMPT-CSS treatment planning significantly reduced radiation dose to cardiac substructures. The significant improvements outlined in this study for proton therapy suggest possible clinical improvement in alignment with previous analyses of CSS optimization.

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Clinical Intensity Modulated Proton Therapy for Hodgkin Lymphoma: Which Patients Benefit the Most?

Cited by 30 publications

References 24 publications

Intensity modulated proton therapy compared to volumetric modulated arc therapy in the irradiation of young female patients with hodgkin’s lymphoma. Assessment of risk of toxicity and secondary cancer induction

Intensity modulated proton therapy compared to volumetric modulated arc therapy in the irradiation of young female patients with hodgkin’s lymphoma. Assessment of risk of toxicity and secondary cancer induction

Advantage of proton-radiotherapy for pediatric patients and adolescents with Hodgkin’s disease

Reducing Heart Dose with Protons and Cardiac Substructure Sparing for Mediastinal Lymphoma Treatment

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