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Charged particle therapy—optimization, challenges and future directions

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.

Key Points

  • Charged particle therapy (CPT) is an emerging technique in radiotherapy, with several new centres under construction worldwide, despite their high cost compared to conventional X-ray therapy

  • Protons are ideal for conformal treatment, and are useful for treating paediatric tumours; reduced late morbidity is expected because of the lower integral dose to the normal tissue

  • Heavy ions (carbon) provide physical and biological advantages compared with X-rays, such as high relative biological effectiveness and reduced oxygen enhancement ratio in the tumour region

  • Clinical trials are still too scarce to draw firm conclusions on the cost effectiveness of CPT

  • Spot-scanning provides the best dose profiles compared with passive beam modulation, but requires corrections for treating moving targets

  • Research in radiobiology and combined therapies is necessary to define the optimum tumours to be treated with CPT

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Figure 1: Dose-escalation for skull-base chordomas.
Figure 2: Measurement of a distal dose in anthropomorphic phantom (MATROSHKA), where a virtual brain tumour was treated with IMRT and CPT using either scanning or passive modulation in different facilities.
Figure 3: An example of single-fraction treatment plan for a patient with non-small-cell lung cancer.
Figure 4: Proton treatment plan at Massachusetts General Hospital for a 16-year-old boy with a co-secreting growth hormone and prolactin pituitary adenoma status post partial resection via transphenoidal approach presented with hypogonadism and right proptosis and accelerated vertical growth.
Figure 5: Proton treatment plan at Massachusetts General Hospital for 56-year-old man presenting with sixth nerve palsy and hypopituitarism, a benign meningioma.
Figure 6: Treatment of moving targets with scanning beams.
Figure 7: RBE versus LET from published experiments on in vitro cell lines.

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Acknowledgements

We thank Michael Scholz, Christoph Bert, Christian Graeff, and Thomas Friedrich for providing some of the figures.

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M. Durante researched the data for the article and wrote the article. Both authors made a substantial contribution to discussion of content and J. S. Loeffler reviewed and edited the manuscript before submission.

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Correspondence to Marco Durante.

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J. S. Loeffler declares he is on the Scientific Advisory Board of Procure. M. Durante declares no competing interests.

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Loeffler, J., Durante, M. Charged particle therapy—optimization, challenges and future directions. Nat Rev Clin Oncol 10, 411–424 (2013). https://doi.org/10.1038/nrclinonc.2013.79

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