A systematic literature review of the clinical and cost-effectiveness of hadron therapy in cancer

Lodge, Mark; Pijls‐Johannesma, Madelon; Stirk, Lisa; Munro, Alastair J.; Ruysscher, Dirk De; Jefferson, Tom

doi:10.1016/j.radonc.2007.04.007

Cited by 130 publications

(76 citation statements)

References 99 publications

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“…While evidence based medicine is concerned with weighing Level I evidence for or against a given intervention, LEBM is concerned with the systematic reviewing of the Lack-of-level-I evidence on a given topic. In the May 2007 issue of Radiotherapy & Oncology, two overviews and an invited editorial, running over a total of 28 pages, summarized the lack of Level I evidence for a benefit from proton therapy [18][19][20]. Add to this, that the same body of non-evidence underwent systematic review in the March 10, 2007 issue of Journal of Clinical Oncology [21] and in part by Widesott et al in this issue of the Journal, and it is clear, that proton LEBM is a current hot topic.…”

Section: Lack-of-evidence Based Medicinementioning

confidence: 99%

“…It just documents the widelyappreciated fact among anyone interested in the field, that there is no major body of randomized trials comparing protons with photons, and as suggested by Glimelius and Montelius [20], perhaps for good reasons. Still, it is concluded that "existing data do not suggest that the rapid expansion of hadron therapy as a major treatment modality would be appropriate" and "the introduction…of hadron therapy as a major treatment modality… into standard clinical patient care cannot be supported by the evidence base currently available" which is logically correct but can easily be mistaken as evidence against protons [18]. Again, there is an important difference between a lack of effect estimates vs. estimates showing a lack of effect!…”

Section: Lack-of-evidence Based Medicinementioning

confidence: 99%

“…Now, to the extent that there is uncertainty regarding the benefits of proton or light-ion therapy compared with photons, this relates to the clinical magnitude of the therapeutic benefit rather than to the principal dosimetric advantage of these radiation modalities. It is clear, just from the reviews published in this journal [18][19][20] This is where individual equipoise enters the equation. A randomized trial allocating patients to proton vs. photon therapy can by necessity only be conducted in centers with proton therapy facilities and proton therapy expertise.…”

Section: Whose Equipoise?mentioning

confidence: 99%

“…The proton skeptics often bring health economics into the picture arguing that protons are unlikely to be cost-effective compared with photons in several sites [18,42,43]. However, the detailed assumptions of a cost-effectiveness estimation -in the absence of precise differential cost-effectiveness data from a randomized phase III trial with individual patientlevel cost data -will critically affect the conclusions and a number of similar exercises have come out favorably for proton therapy [44][45][46].…”

Section: Health Economics and Technology Assessmentmentioning

confidence: 99%

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Randomized controlled trials in health technology assessment: Overkill or overdue?

Bentzen

2008

Radiotherapy and Oncology

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Evidence-based medicine has become a cornerstone in the development of radiation oncology and the randomized controlled phase III trial remains the gold standard for assessing differential benefits in clinical outcome between therapies. Health technologies aimed at improving treatment quality should primarily be tested using process measures or operational characteristics, the reason being that the sensitivity and specificity of clinical outcome is low for detecting quality improvements. The ongoing discussion of the relative merits of intensity modulated photon vs. proton radiotherapy is used to illustrate these concepts. Concerns over clinical and individual equipoise as well as the potential limitations of health economics considerations in this setting are also discussed. Working in a technology and science based medical discipline, radiation oncology researchers need to further develop methodology for critical assessment of health technologies as a complement to randomized controlled trials."Only two options exist. The first is that we accept that, under exceptional circumstances, common sense might be applied when considering the potential risks and benefits of interventions. The second is that we continue our quest for the holy grail of exclusively evidence based interventions and preclude parachute use outside the context of a properly conducted trial." Evidence-based medicine and randomized controlled trialsEvidence-based medicine is a compelling paradigm as a rational road-map, some would argue the only rational road-map, for improving the standard of health care [2,3]. The role of randomized controlled trials in this context cannot be overstated: while the allocation to different treatment options may be skewed even in a specific randomized trial, randomization is the only method that on average safe-guards against prognostic imbalances that could bias therapy effect estimates. History shows, that even when there has been overwhelming support for a novel therapeutic intervention in terms of a well-proven mechanism of action, promising pre-clinical and early clinical data as well as wide-spread consensus regarding an expected benefit among the experts, the cold-hearted scrutiny of a,

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Section: Lack-of-evidence Based Medicinementioning

confidence: 99%

Section: Lack-of-evidence Based Medicinementioning

confidence: 99%

Section: Whose Equipoise?mentioning

confidence: 99%

Section: Health Economics and Technology Assessmentmentioning

confidence: 99%

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Randomized controlled trials in health technology assessment: Overkill or overdue?

Bentzen

2008

Radiotherapy and Oncology

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“…Although clinical results comparing proton therapy with the most modern X-ray therapy are currently lacking, overall clinical outcomes are promising for both delivery options and support the rationale for proton therapy [8]. The reader is referred to the literature [9][10][11] for more clinical data. Nevertheless, substantial opportunity for further clinical research development and evaluation remains.…”

mentioning

confidence: 99%

Treatment planning optimisation in proton therapy

McGowan¹,

Burnet²,

Lomax³

2013

BJR

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ABSTRACT. The goal of radiotherapy is to achieve uniform target coverage while sparing normal tissue. In proton therapy, the same sources of geometric uncertainty are present as in conventional radiotherapy. However, an important and fundamental difference in proton therapy is that protons have a finite range, highly dependent on the electron density of the material they are traversing, resulting in a steep dose gradient at the distal edge of the Bragg peak. Therefore, an accurate knowledge of the sources and magnitudes of the uncertainties affecting the proton range is essential for producing plans which are robust to these uncertainties. This review describes the current knowledge of the geometric uncertainties and discusses their impact on proton dose plans. The need for patient-specific validation is essential and in cases of complex intensity-modulated proton therapy plans the use of a planning target volume (PTV) may fail to ensure coverage of the target. In cases where a PTV cannot be used, other methods of quantifying plan quality have been investigated. A promising option is to incorporate uncertainties directly into the optimisation algorithm. A further development is the inclusion of robustness into a multicriteria optimisation framework, allowing a multi-objective Pareto optimisation function to balance robustness and conformity. The question remains as to whether adaptive therapy can become an integral part of a proton therapy, to allow re-optimisation during the course of a patient's treatment. The challenge of ensuring that plans are robust to range uncertainties in proton therapy remains, although these methods can provide practical solutions. The ability to create and deliver the ideal treatment plan, where the target volume receives 100% of the prescribed dose and normal tissue receives 0%, is the holy grail of radiation therapy [1]. It is, however, impossible to achieve this perfect balance. Instead, multiple trade-offs are required to achieve a clinically acceptable plan, so the problem becomes one of optimisation. There are many factors that can affect how ''optimised'' a patient's treatment can be. This review focuses on the challenges of proton therapy plan optimisation, particularly in regard to range uncertainties, and how to incorporate them into the plan evaluation and verification process.The nature of proton therapy makes the aim of cure without complications potentially more achievable, owing to the highly localised deposition of dose in the characteristic Bragg peak [2]. This relates predominantly to the ability to deliver high doses of radiation close to normal tissue structures, which would be dose limiting in conventional X-ray treatments, and to the finite range of protons, which results in a reduced integral dose to surrounding normal tissues.From a clinical perspective, the exact role of proton therapy has yet to be defined. However, for childhood cancers, proton therapy delivers a lower dose to tissues around the tumour than X-rays, resulting in less growth disturbance and l...

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