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General medicine
Trial supports targeted radiotherapy for early breast cancer but protocol still requires 3 weeks of daily therapy
  1. Jayant S Vaidya1,
  2. Frederik Wenz2,
  3. Jeffrey S Tobias3
  1. 1 Division of Surgery and Interventional Science, University College London, London
  2. 2 Department of Radiation Oncology, University of Heidelberg, Mannheim, Germany
  3. 3 Department of Clinical Oncology, University College London, London, UK
  1. Correspondence to Professor Jayant S Vaidya, Division of Surgery and Interventional Science, University College London, London W1W 7JN, UK; jayant.vaidya{at}ucl.ac.uk

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Commentary on: Coles CE, Griffin CL, Kirby AM, et al. IMPORT Trialists. Partial-breast radiotherapy after breast conservation surgery for patients with early breast cancer (UK IMPORT LOW trial): 5-year results from a multicentre, randomised, controlled, phase 3, non-inferiority trial. Lancet 2017;390:1048–60.

Context

The evidence-based local treatment for early breast cancer is breast-conserving surgery and radiotherapy, requiring 3–6 weeks of daily whole breast external beam radiation therapy, which is inconvenient for patients and expensive.

The suggestion that targeted radiation to the tumour bed with modern techniques may be adequate was proposed in 1995.1 This was heralded as a new standard2 with the publication of the TARGIT-A trial3 4 of single-dose targeted intraoperative radiotherapy (TARGIT-IORT), later confirmed by other European studies using brachytherapy5 that requires 5 days of inpatient stay or EBRT.6

Methods

In this study,7 in 30 UK centres, from 2007 to 2010, women aged ≥50 years, who had undergone breast-conserving surgery for unifocal invasive ductal carcinoma ≤3 cm in size with a 2 mm non-cancerous excision margin, were randomly assigned (1:1:1) to receive daily over 3 weeks one of three regimens: (1) 40 Gy whole breast irradiation (WBI); (2) 36 Gy WBI with 40 Gy partial breast irradiation (PBI); or (3) 40 Gy PBI targeted to the tumour bed. The primary endpoint was ipsilateral local relapse with a non-inferiority margin of 2.5% at 5 years. For quality of life, 72 different patient-reported outcome measures (PROM) were analysed and radiotherapy toxicity was assessed by photographs and clinicians. Neither patients, clinicians nor data analysts were masked to treatment allocation.

Findings

Five-year estimated incidence of local relapse was 1.1% (95% CI 0.5 to 2.3) with WBI (n=674) and 0.5% (0.2–1.4) with PBI (n=669); non-inferiority was confirmed.

Unlike in prior trials,3–6 radiotherapy toxicity was not reduced. Of the 72 PROMs assessed, only two (breast appearance and texture) were reported to have better cumulative scores with PBI. The incidence of only one PROM (‘breast appearance changed’) was reduced at 5 years (from 27% to 15%).

Commentary

IMPORT-LOW provides further mature randomised evidence supporting PBI. However, PBI with IMPORT-LOW protocol offers little advantage to patients or the healthcare system. The 2 mm clear margins this protocol requires render many patients ineligible; acceptable margins are currently much smaller, for example, >0 mm in USA.8 The authors emphasise the benefit in two quality of life domains, although 72 were tested, with 5-year benefit seen in only one.

Clearly, IMPORT-LOW patients had considerably better prognosis cancers than in other trials that have proven non-inferiority of targeted radiation to whole breast radiation. Compared with TARGIT-A, for example, only 3% versus 16% were node positive, and 9% versus 15% were grade 3. Therefore, the low recurrence rate is not surprising.

Who benefits from the IMPORT-LOW protocol? For patients and healthcare systems, the 3-week daily regimen has adverse physical, social, financial9 and environmental impacts10 and offers no advantage over conventional radiation. PBI using IMPORT-LOW is also resource consuming (and therefore expensive), and keeps radiotherapy departments very busy. Conversely, TARGIT-IORT delivered during the operation enables over 80% of patients to avoid visiting the radiotherapy centre at all. The relevance here is that although published twice in The Lancet, with an independent editorial concluding that it should be offered as an alternative to conventional EBRT, TARGIT-IORT is not even mentioned in the IMPORT-LOW paper. We find this surprising since the number of patients with a median follow-up of 5–6 years is similar (~1200 vs 1300), and both proved non-inferiority.

Implications for practice

Targeted radiation methods range from the 3-week daily course required for IMPORT-LOW with 16 hospital visits, to the single-dose TARGIT-IORT given during lumpectomy. Several other approaches are also available,5 6 and as all are effective, patients are entitled to choose what is right for them, based on convenience, personal cost, quality of life and side effects.

Acknowledgments

We thank Professor Michael Baum, Professor Michael Douek, Mr Nathan Coombs, Professor Max Bulsara, Dr Julian Singer, Dr David Morgan, Dr Shiroma D’Silva and Ms Marcelle Bernstein for valuable discussion about this manuscript.

References

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Footnotes

  • Contributors JSV wrote the initial draft. JST and FW made contributions to the draft. All authors approved the final manuscript.

  • Competing interests Carl Zeiss has sponsored some travel to some conferences and has paid some honoraria.

  • Provenance and peer review Commissioned; internally peer reviewed.

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