Use of ‘sham’ radiotherapy in randomized clinical trials

Schwarz, Fabian; Christie, David

doi:10.1111/j.1440-1673.2008.01936.x

Cited by 5 publications

(3 citation statements)

References 47 publications

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“…The absence of treatment blinding is always a limitation for subjective endpoints, such as toxicity. Although blinding has been achieved in previous radiotherapy trials, 26,27 it is not feasible for most studies. We also note the higher fiducial marker use for image-guided radio therapy in patients undergoing stereo tactic body radiotherapy compared with conventionally fractionated or moderately hypo fractionated radiotherapy in PACE-B.…”

Section: Discussionmentioning

confidence: 99%

Intensity-modulated fractionated radiotherapy versus stereotactic body radiotherapy for prostate cancer (PACE-B): acute toxicity findings from an international, randomised, open-label, phase 3, non-inferiority trial

Brand¹,

Tree²,

Ostler³

et al. 2019

The Lancet Oncology

412

338

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SummaryBackgroundLocalised prostate cancer is commonly treated with external-beam radiotherapy. Moderate hypofractionation has been shown to be non-inferior to conventional fractionation. Ultra-hypofractionated stereotactic body radiotherapy would allow shorter treatment courses but could increase acute toxicity compared with conventionally fractionated or moderately hypofractionated radiotherapy. We report the acute toxicity findings from a randomised trial of standard-of-care conventionally fractionated or moderately hypofractionated radiotherapy versus five-fraction stereotactic body radiotherapy for low-risk to intermediate-risk localised prostate cancer.MethodsPACE is an international, phase 3, open-label, randomised, non-inferiority trial. In PACE-B, eligible men aged 18 years and older, with WHO performance status 0–2, low-risk or intermediate-risk prostate adenocarcinoma (Gleason 4 + 3 excluded), and scheduled to receive radiotherapy were recruited from 37 centres in three countries (UK, Ireland, and Canada). Participants were randomly allocated (1:1) by computerised central randomisation with permuted blocks (size four and six), stratified by centre and risk group, to conventionally fractionated or moderately hypofractionated radiotherapy (78 Gy in 39 fractions over 7·8 weeks or 62 Gy in 20 fractions over 4 weeks, respectively) or stereotactic body radiotherapy (36·25 Gy in five fractions over 1–2 weeks). Neither participants nor investigators were masked to allocation. Androgen deprivation was not permitted. The primary endpoint of PACE-B is freedom from biochemical or clinical failure. The coprimary outcomes for this acute toxicity substudy were worst grade 2 or more severe Radiation Therapy Oncology Group (RTOG) gastrointestinal or genitourinary toxic effects score up to 12 weeks after radiotherapy. Analysis was per protocol. This study is registered with ClinicalTrials.gov, NCT01584258. PACE-B recruitment is complete and follow-up is ongoing.FindingsBetween Aug 7, 2012, and Jan 4, 2018, we randomly assigned 874 men to conventionally fractionated or moderately hypofractionated radiotherapy (n=441) or stereotactic body radiotherapy (n=433). 432 (98%) of 441 patients allocated to conventionally fractionated or moderately hypofractionated radiotherapy and 415 (96%) of 433 patients allocated to stereotactic body radiotherapy received at least one fraction of allocated treatment. Worst acute RTOG gastrointestinal toxic effect proportions were as follows: grade 2 or more severe toxic events in 53 (12%) of 432 patients in the conventionally fractionated or moderately hypofractionated radiotherapy group versus 43 (10%) of 415 patients in the stereotactic body radiotherapy group (difference −1·9 percentage points, 95% CI −6·2 to 2·4; p=0·38). Worst acute RTOG genitourinary toxicity proportions were as follows: grade 2 or worse toxicity in 118 (27%) of 432 patients in the conventionally fractionated or moderately hypofractionated radiotherapy group versus 96 (23%) of 415 patients in the stereotactic body radioth...

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Section: Discussionmentioning

confidence: 99%

Intensity-modulated fractionated radiotherapy versus stereotactic body radiotherapy for prostate cancer (PACE-B): acute toxicity findings from an international, randomised, open-label, phase 3, non-inferiority trial

Brand¹,

Tree²,

Ostler³

et al. 2019

The Lancet Oncology

412

338

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“…There have been a number of clinical studies involving the use of external beam radiotherapy as a possible nonsurgical treatment or ARMD where 10-20 Gy is delivered to the macula in 2 -3 Gy fractions. 19 Some have produced results of reduction in vision loss, whereas others have failed to show any benefit, and in some cases have shown deleterious effects, such as cataract formation and xerophthalmia. Nevertheless, there have been sufficient pilot clinical studies to suggest that photon radiotherapy may be a viable option to treat ARMD if higher fractions ͑Ͼ4 Gy͒ can be applied to the macula target, simultaneously limiting nontarget tissue toxicity.…”

Section: Introductionmentioning

confidence: 99%

Dosimetry characterization of a multibeam radiotherapy treatment for age‐related macular degeneration

Lee

Chell²,

Gertner³

et al. 2008

Medical Physics

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Age-related macular degeneration (ARMD) is a major health problem worldwide. Advanced ARMD, which ultimately leads to profound vision loss, has dry and wet forms, which account for 20% and 80% of cases involving severe vision loss, respectively. A new device and approach for radiation treatment of ARMD has been recently developed by Oraya Therapeutics, Inc. (Newark, CA). The goal of the present study is to provide a initial dosimetry characterization of the proposed radiotherapy treatment via Monte Carlo radiation transport simulation. A 3D eye model including cornea, anterior chamber, lens, orbit, fat, sclera, choroid, retina, vitreous, macula, and optic nerve was carefully designed. The eye model was imported into the MCNPX2.5 Monte Carlo code and radiation transport simulations were undertaken to obtain absorbed doses and dose volume histograms (DVH) to targeted and nontargeted structures within the eye. Three different studies were undertaken to investigate (1) available beam angles that maximized the dose to the macula target tissue, simultaneously minimizing dose to normal tissues, (2) the energy dependency of the DVH for different x-ray energies (80, 100, and 120 kVp), and (3) the optimal focal spot size among options of 0.0, 0.4, 1.0, and 5.5 mm. All results were scaled to give 8 Gy to the macula volume, which is the current treatment requirement. Eight beam treatment angles are currently under investigation. In all eight beam angles, the source-to-target distance is 13 cm, and the polar angle of entry is 300 from the geometric axis of the eye. The azimuthal angle changes in eight increments of 45 degrees in a clockwise fashion, such that an azimuthal angle of 0 degreee corresponds to the 12 o'clock position when viewing the treated eye. Based on considerations of nontarget tissue avoidance, as well as facial-anatomical restrictions on beam delivery, treatment azimuthal angles between 135 degrees and 225 degrees would be available for this treatment system (i.e., directly upward and entering the eye from below). At beam directions approaching 225 degrees and higher, some dose contribution to the optic nerve would result under the assumption that the optic nerve is tilted cranially above the geometric axis in a given patient, a feature not typically seen in past studies. A total treatment dose of 24 Gy would be delivered in three 8 Gy treatments at these selected azimuthal angles. Dose coefficients, defined as the macula radiation absorbed dose per unit air kerma in units of Gy/Gy, were 16% higher for 120 kVp x-ray beams in comparison to those at 80 kVp, thus requiring only 86% of the integrated tube current (mAs) for equivalent dose delivery. When 0.0, 0.4, and 1.0 mm focal spot sizes were used, the dose profiles in the macula are very similar and relatively uniform, whereas a 5.5 mm focal spot size produced a more nonuniform dose profile. The results of this study dem onstrate the therapeutic promise of this device and provide important information for further design and clinical implementation for radio...

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“…The reliance on new technologies within radiation oncology poses unique challenges in generating level I evidence based on randomized controlled data. 19 , 20 Once technology becomes available, the community tends to quickly adopt certain practices based on technological benefits before proof of patient benefit is derived from higher level studies. In addition, the field of radiation oncology is grossly underfunded in the United States relative to its role in cancer care.…”

Section: Discussionmentioning

confidence: 99%

Levels of Evidence for Radiation Therapy Recommendations in the National Comprehensive Cancer Network (NCCN) Clinical Guidelines

Noy

Rich

Llorente

et al. 2022

Advances in Radiation Oncology

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Purpose The National Comprehensive Cancer Network (NCCN) clinical guidelines influence medical practice, payor coverage, and standards of care. The levels of evidence underlying radiation therapy recommendations in NCCN have not been systematically explored. Herein, we aim to systematically investigate the NCCN recommendations pertaining to the categories of consensus and evidence (CE) for radiation therapy. Methods and Materials We evaluated the distribution of CE underlying current treatment recommendations for the 20 most prevalent cancers in the United States with at least 10 radiation therapy recommendations in the NCCN clinical guidelines. For context, the distribution of evidence in the radiation therapy guidelines was compared with that of systemic therapy using a χ 2 test. The proportion of category I CE between radiation and systemic therapy was compared using a 2-proportion, 2-tailed z-test in total and for each disease site. A P value of < .05 was considered significant. Results Among all radiation therapy recommendations, the proportions of category I, IIA, IIB, and III CE were 9.7%, 80.6%, 8.4%, and 1.3%, respectively. When analyzed by disease site, cervix and breast cancer had the highest portion of category I CE (33% and 31%, respectively). There was no radiation therapy category I CE for hepatobiliary, bone, pancreatic, melanoma, and uterine cancers. There was a significant difference in the distribution of CE between the systemic therapy recommendations and the radiation therapy recommendations (χ 2 statistic 64.16, P < .001). Overall, there was a significantly higher proportion of category I CE in the systemic therapy recommendations compared with the radiation therapy recommendations (12.3% vs 9.7%, P = .043). Conclusions Only 9.7% of radiation therapy recommendations in NCCN guidelines are category I CE. The highest levels of evidence for radiation therapy are in breast and cervical cancers. Despite major advances in the field, these data underline that the majority of NCCN radiation therapy recommendations are based on uniform expert opinion and not on higher level evidence.

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Use of ‘sham’ radiotherapy in randomized clinical trials

Cited by 5 publications

References 47 publications

Intensity-modulated fractionated radiotherapy versus stereotactic body radiotherapy for prostate cancer (PACE-B): acute toxicity findings from an international, randomised, open-label, phase 3, non-inferiority trial

Intensity-modulated fractionated radiotherapy versus stereotactic body radiotherapy for prostate cancer (PACE-B): acute toxicity findings from an international, randomised, open-label, phase 3, non-inferiority trial

Dosimetry characterization of a multibeam radiotherapy treatment for age‐related macular degeneration

Levels of Evidence for Radiation Therapy Recommendations in the National Comprehensive Cancer Network (NCCN) Clinical Guidelines

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