Improving the therapeutic ratio in Hodgkin lymphoma through the use of proton therapy

University of Florida Proton Therapy Institute, Jacksonville, Florida 32206, USA.
Oncology (Williston Park, N.Y.) (Impact Factor: 2.32). 05/2012; 26(5):456-9, 462-5.
Source: PubMed


The risk of serious late complications in Hodgkin lymphoma (HL) survivors has led to a variety of strategies for reducing late treatment effects from both chemotherapy and radiation therapy. With radiation therapy, efforts have included reductions in dose, reductions in the size of the target volume, and most recently, significant reductions in the dose to nontargeted normal tissues at risk for radiation damage, achieved by using the emerging technologies of intensity-modulated radiation therapy and proton therapy (PT). PT is associated with a substantial reduction in radiation dose to critical organs, such as the heart and lungs, and has the potential to improve not only the therapeutic ratio, but also both event-free and overall survival. This review addresses the rationale and evidence for--and the challenges, cost implications, and future development of--PT as an important part of the treatment strategy in HL.

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    • "was scaled to high values, indicating that the predicted risk of cardiac toxicity from proton therapy may be higher than that from photon therapy if the RBE of stray neutrons is large. While the advantage of proton therapy is not obvious in terms of reducing cardiac toxicity for this HD patient, the lower out-of-field dose would possibly decrease risks of other late effects [32,33]. It is possible that risk from proton therapy could be reduced if IMPT were used rather than PSPT. "
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    ABSTRACT: Hodgkin disease (HD) and medulloblastoma (MB) are common malignancies found in children and young adults, and radiotherapy is part of the standard treatment. It was reported that these patients who received radiation therapy have an increased risk of cardiovascular late effects. We compared the predicted risk of developing radiogenic cardiac toxicity after photon versus proton radiotherapies for a pediatric patient with HD and a pediatric patient with MB. In the treatment plans, each patient's heart was contoured in fine detail, including substructures of the pericardium and myocardium. Risk calculations took into account both therapeutic and stray radiation doses. We calculated the relative risk (RR) of cardiac toxicity using a linear risk model and the normal tissue complication probability (NTCP) values using relative seriality and Lyman models. Uncertainty analyses were also performed. The RR values of cardiac toxicity for the HD patient were 7.27 (proton) and 8.37 (photon), respectively; the RR values for the MB patient were 1.28 (proton) and 8.39 (photon), respectively. The predicted NTCP values for the HD patient were 2.17% (proton) and 2.67% (photon) for the myocardium, and were 2.11% (proton) and 1.92% (photon) for the whole heart. The predicted ratios of NTCP values (proton/photon) for the MB patient were much less than unity. Uncertainty analyses revealed that the predicted ratio of risk between proton and photon therapies was sensitive to uncertainties in the NTCP model parameters and the mean radiation weighting factor for neutrons, but was not sensitive to heart structure contours. The qualitative findings of the study were not sensitive to uncertainties in these factors. We conclude that proton and photon radiotherapies confer similar predicted risks of cardiac toxicity for the HD patient in this study, and that proton therapy reduced the predicted risk for the MB patient in this study.
    Radiation Oncology 07/2013; 8(1):184. DOI:10.1186/1748-717X-8-184 · 2.55 Impact Factor
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    • "With the same purpose Tomotherapy has been recently proposed for the treatment of HL [8]. Recent preliminary studies of proton beam therapy for mediastinal HL have been reported [4]. The OARs toxicities and development of second breast neoplasms would be expected to be reduced by the use of particle therapy. "
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    ABSTRACT: Background Purpose of this study is to explore the trade-offs between radio-induced toxicities and second malignant neoplasm (SMN) induction risk of different emerging radiotherapy techniques for Hodgkin’s lymphoma (HL) through a comprehensive dosimetric analysis on a representative clinical model. Methods Three different planning target volume (PTVi) scenarios of a female patient with supradiaphragmatic HL were used as models for the purpose of this study. Five treatment radiation techniques were simulated: an anterior-posterior parallel-opposed (AP-PA), a forward intensity modulated (FIMRT), an inverse intensity modulated (IMRT), a Tomotherapy (TOMO), a proton (PRO) technique. A radiation dose of 30 Gy or CGE was prescribed. Dose-volume histograms of PTVs and organs-at-risk (OARs) were calculated and related to available dose-volume constraints. SMN risk for breasts, thyroid, and lungs was estimated through the Organ Equivalent Dose model considering cell repopulation and inhomogeneous organ doses. Results With similar level of PTVi coverage, IMRT, TOMO and PRO plans generally reduced the OARs’ dose and accordingly the related radio-induced toxicities. However, only TOMO and PRO plans were compliant with all constraints in all scenarios. For the IMRT and TOMO plans an increased risk of development of breast, and lung SMN compared with AP-PA and FIMRT techniques was estimated. Only PRO plans seemed to reduce the risk of predicted SMN compared with AP-PA technique. Conclusions Our model–based study supports the use of advanced RT techniques to successfully spare OARs and to reduce the risk of radio-induced toxicities in HL patients. However, the estimated increase of SMNs’ risk inherent to TOMO and IMRT techniques should be carefully considered in the evaluation of a risk-adapted therapeutic strategy.
    Radiation Oncology 01/2013; 8(1):22. DOI:10.1186/1748-717X-8-22 · 2.55 Impact Factor
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    ABSTRACT: The use of charged particle therapy to control tumours non-invasively offers advantages over conventional radiotherapy. Protons and heavy ions deposit energy far more selectively than X-rays, allowing a higher local control of the tumour, a lower probability of damage to healthy tissue, low risk of complications and the chance for a rapid recovery after therapy. Charged particles are also useful for treating tumours located in areas that surround tissues that are radiosensitive and in anatomical sites where surgical access is limited. Current trial outcomes indicate that accelerated ions can potentially replace surgery for radical cancer treatments, which might be beneficial as the success of surgical cancer treatments are largely dependent on the expertise and experience of the surgeon and the location of the tumour. However, to date, only a small number of controlled randomized clinical trials have made comparisons between particle therapy and X-rays. Therefore, although the potential advantages are clear and supported by data, the cost:benefit ratio remains controversial. Research in medical physics and radiobiology is focusing on reducing the costs and increasing the benefits of this treatment.
    Nature Reviews Clinical Oncology 05/2013; 10(7). DOI:10.1038/nrclinonc.2013.79 · 14.18 Impact Factor
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