A randomised controlled trial of forward-planned radiotherapy (IMRT) for early breast cancer: Baseline characteristics and dosimetry results
Department of Oncology, University of Cambridge, Cambridge, UK. Radiotherapy and Oncology
(Impact Factor: 4.36).
04/2009; 92(1):34-41. DOI: 10.1016/j.radonc.2009.03.003
This large trial was designed to investigate whether correction of dose inhomogeneities using intensity-modulated radiotherapy (IMRT) reduces late toxicity and improves quality of life in patients with early breast cancer. This paper reports baseline characteristics of trial participants and dosimetry results.
Standard tangential plans of 1145 trials were analysed. Patients with inhomogeneous plans, defined by ICRU recommendations, were randomised to forward-planned IMRT or standard radiotherapy.
Twenty-nine percentage of patients had adequate dosimetry with standard 2D radiotherapy. In the randomised patients, the decreases in mean volumes receiving greater than 107% (Vol>107) and less than 95% (Vol<95) of the prescribed dose in the IMRT compared with the control group were 34.0 cm(3) (95% CI 26.4-41.6; P<0.0001) and 48.1 cm(3) (95% CI 34.4-61.9; P<0.0001), respectively. In this study, 90% of patients who had a breast separation greater > or = 21 cm had Vol>107>2 cm(3) on standard radiotherapy plans.
This large trial, in which patients with all breast sizes were eligible, confirmed that breast dosimetry can be significantly improved with a simple method of forward-planned IMRT and has little impact on radiotherapy resources. It is shown that patients with larger breasts are more likely to have dose inhomogeneities and breast separation gives some indication of this likelihood. Photographic assessment of patients at 2 years after radiotherapy, as the next part of this randomised controlled trial, will show whether these results for IMRT translate into improved cosmetic outcome in patients with early breast cancer. This would provide impetus for the widespread adoption of 3D planning and IMRT.
Available from: Jean-Pierre Bissonnette
- "Veldeman conducted a systematic review of the clinical evidence for IMRT in 2008 which included 56 comparative studies, 3 of which were randomized controlled trials (RCTs) , and concluded that IMRT reduced treatment-related toxic effects and improved quality of life. A second systematic review in 2010  reported reduced acute and late toxicity associated with IMRT [4-10,12,13]. Three RCTs reported significant improvement of acute xerostomia with the use of IMRT in head and neck cancers and better quality of life [6,7,9,13], and IMRT for breast cancer was also associated with reduced acute and late side effects when compared to 2D RT in three RCTs [4,5,8]. With further RCTs in progress , additional evidence will soon be available. "
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ABSTRACT: The timely and appropriate adoption of new radiation therapy (RT) technologies is a challenge both in terms of providing of optimal patient care and managing health care resources. Relatively little is known regarding the rate at which new RT technologies are adopted in different jurisdictions, and the barriers to implementation of these technologies.
Surveys were sent to all radiation oncology department heads in Canada regarding the availability of RT equipment from 2006 to 2010. Data were collected concerning the availability and use of Intensity Modulated Radiation Therapy (IMRT) and stereotactic radiosurgery (SRS), and the obstacles to implementation of these technologies.
IMRT was available in 37% of responding centers in 2006, increasing to 87% in 2010. In 2010, 72% of centers reported that IMRT was available for all patients who might benefit, and 37% indicated that they used IMRT for "virtually all" head and neck patients. SRS availability increased from 26% in 2006 to 42.5% in 2010. Eighty-two percent of centers reported that patients had access to SRS either directly or by referral. The main barriers for IMRT implementation included the need to train or hire treatment planning staff, whereas barriers to SRS implementation mostly included the need to purchase and/or upgrade existing planning software and equipment.
The survey showed a growing adoption of IMRT and SRS in Canada, although the latter was available in less than half of responding centers. Barriers to implementation differed for IMRT compared to SRS. Enhancing human resources is an important consideration in the implementation of new RT technologies, due to the multidisciplinary nature of the planning and treatment process.
Available from: Mark A Sydenham
- "In the patients with any volumes receiving >107%, the median percentage volume of treated breast receiving dose >107% was extremely small (0.1%). This figure for partial breast volumes receiving >107% of prescribed dose is consistent with previous reports in the literature . The distribution of volume receiving >100% dose was split into quartiles for the analysis assessing the effect of dosimetry on risk of late adverse effects. "
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ABSTRACT: Large breast size is associated with an increased risk of late adverse effects after breast conservation surgery and radiotherapy, even when 3D dosimetry is used. The purpose of this study is to test the hypothesis that residual dose inhomogeneity is sufficient to explain the association.
Patients previously treated after breast conservation surgery with whole breast radiotherapy using 3D dosimetry and followed up in the UK FAST hypofractionation trial were selected for this analysis. The residual level of dose inhomogeneity across the whole breast treatment volume was used to test for association between residual dosimetry and post-treatment change in breast appearance at 2 years post-radiotherapy.
At 2 years, 201/279 (72%) of women had no change in photographic breast appearance, 61 (22%) had mild change and 17 (6%) had marked change. Breast size and dosimetry were both significantly associated with late effects in univariate analyses, but only breast size remained an independent significant risk factor for change in breast appearance when included in a multiple regression model together with other prognostic factors (p=0.006 for trend).
Large-breasted women are more likely to suffer change in breast size and shape after whole breast radiotherapy delivered using 3D dosimetry, but residual dose inhomogeneity is insufficient to explain the association.
Available from: ncbi.nlm.nih.gov
- "An energy of 6 MV was used in most patients, but mixed energies of 6 and 15 MV photons were used when required in patients with larger separations. Nodal radiotherapy and a tumour bed boost were administered according to local protocols . A boost was given to all patients except those deemed at low risk with all of the following: age >50 years, T1 stage, Grade 1 or 2, absence of lymph node metastases (including micrometastases), no lymphovascular space invasion, margins ≥5 mm (or 2 mm if anterior or deep margin and no more tissue to take). "
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ABSTRACT: Several small studies have reported associations between TGFB1 single nucleotide polymorphisms (SNPs), considered to increase secretion of TGF-β1, and greater than 3-fold increases in incidence of fibrosis - an indicator of late toxicity after radiotherapy in breast cancer patients.
Two SNPs in TGFB1, C-509T (rs1800469) and L10P (rs1800470), were genotyped in 778 breast cancer patients who had received radiotherapy to the breast. Late radiotherapy toxicity was assessed two years after radiotherapy using a validated photographic technique, clinical assessment and patient questionnaires.
On photographic assessment, 210 (27%) patients showed some degree of breast shrinkage, whilst 45 (6%) patients showed marked breast shrinkage. There was no significant association of genotype at either of the TGFB1 SNPs with any measure of late radiation toxicity.
This adequately powered trial failed to confirm previously reported increases in fibrosis with TGFB1 genotype - any increase greater than 1.36 can be excluded with 95% confidence. Similar frequent failures to replicate associations with candidate genes have been resolved using genome-wide association scans: this methodology detects common, low risk alleles but requires even larger patient numbers for adequate statistical power.
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