A large, 10-year, randomized clinical trial - called TARGIT-A - has revealed promising results for the broadening use of a shorter and easier radiation therapy method for patients with breast cancer. The study revealed that a single radiation dose during surgery (IORT = infra-operative radiotherapy) is at least as effective as longer post-operative treatments.
In TARGIT (targeted intraoperative radiotherapy) for breast cancer, the radiation therapy is confined to the area of the breast where the tumor has been removed. Researchers reported that TARGIT is as effective at preventing breast cancer recurrence as whole breast radiotherapy; also, it can be carried out in one hospital visit.
This could mean more convenient care for patients, reduced waiting times, and considerable savings for health-care systems.
The findings of the TARGIT-A study are published in an Article Online First and in an upcoming Lancet, and were presented at the American Society of Clinical Oncology (ASCO) meeting in Chicago, USA. The study is by Jayant S Vaidya, University College London, UK, and David Joseph, University of Western Australia, Perth, Australia, and colleagues from 28 centres from 9 countries.
After surgery to conserve the breast, 90% of cancer recurrences occur very near to where the removed tumor was (index quadrant), despite the presence of multicentric cancers elsewhere in the breast. Thus, restriction of radiation therapy to the site of tumor removal (tumour bed) during surgery may be suitable for selected patients. In this study, the authors compared targeted intraoperative radiotherapy with the conventional policy of whole breast external beam radiotherapy.
In this trial, women aged at least 45 years with invasive ductal breast carcinoma undergoing breast-conserving surgery were enrolled. Patients were randomly assigned in a 1:1 ratio to receive targeted intraoperative radiotherapy or whole breast external beam radiotherapy. Postoperative discovery of predefined factors (eg, lobular carcinoma) could trigger addition of external beam radiotherapy to targeted intraoperative radiotherapy (in around 15% of patients). The primary outcome was local recurrence in the conserved breast.
A total of 1113 patients were randomly allocated to targeted intraoperative radiotherapy and 1119 were allocated to external beam radiotherapy.
Of 996 patients who received the allocated treatment in the targeted intraoperative radiotherapy group:
- 854 (86%) received targeted intraoperative radiotherapy only
- 142 (14%) received targeted intraoperative radiotherapy plus external beam radiotherapy
At 4 years, there were:
- 6 local recurrences (of cancer) in the intraoperative radiotherapy group
- 5 local recurrences (of cancer) in the external beam radiotherapy group Meaning the occurrence rates in the two groups were similar; 1•20% in the targeted intraoperative radiotherapy and 0•95% in the external beam radiotherapy group
- Major toxicity - 3.3% in the targeted intraoperative radiotherapy group, and 3•9% in the external beam radiotherapy group.
- Radiation toxicity (Radiation Therapy Oncology Group grade 3) - 0.5% in the targeted intraoperative radiotherapy group, and 2.1% in the external beam radiotherapy group.
- Women aged 45 years or more
- Women with early invasive breast cancer
- Women suitable for breast conserving surgery
- 82% of the patients were less than 70 years of age
In addition to the obvious benefits of completing all the necessary radiotherapy in a single session at the time of surgery, targeted intraoperative radiotherapy almost completely avoids irradiation of the intrathoracic structures such as the heart, lung, and oesophagus. Consequently, the damage to these structures, which can occur even with modern external beam radiotherapy, will have been avoided.
A crucial issue in understanding this trial centres on the benefits to the patient and the effect on the workload of a radiotherapy centre. Treatment of patients with breast cancer accounts for about a third of the workload of radiotherapy departments in some parts of the world and contributes substantially to the unacceptable waiting lists seen in many oncology departments worldwide. In countries such as the UK where the waiting list for postoperative radiotherapy could rapidly diminish with use of targeted intraoperative radiotherapy, we estimate savings of around £15 000 000 (US$23 000 000) a year.
(conclusion) For selected patients with early breast cancer, a single dose of radiotherapy delivered at the time of surgery by use of targeted intraoperative radiotherapy should be considered as an alternative to external beam radiotherapy delivered over several weeks.
In an accompanying Comment, Dr David Azria, Department of Radiation Oncology and INSERM U896, CRLC Val d'Aurelle, Montpellier, France; and Dr Céline Bourgier, Department of Radiation Oncology, Institut Gustave Roussy, Villejuif, France, wrote:
We still await long-term follow-up and the results of another randomised trial from the National Surgical Adjuvant Breast and Bowel Project B-39. Nevertheless, in the elderly, we are already convinced that accelerated partial-breast irradiation is the new standard and intraoperative radiotherapy an excellent approach.
"Targeted intraoperative radiotherapy versus whole breast radiotherapy for breast cancer (TARGIT-A trial): an international, prospective, randomised, non-inferiority phase 3 trial"
Jayant S Vaidya, David J Joseph, Jeffrey S Tobias, Max Bulsara, Frederik Wenz, Christobel Saunders, Michael Alvarado, Henrik L Flyger, Samuele Massarut, Wolfgang Eiermann, Mohammed Keshtgar, John Dewar, Uta Kraus-Tiefenbacher, Marc Sütterlin, Laura Esserman, Helle M R Holtveg, Mario Roncadin, Steffi Pigorsch, Marinos Metaxas, Mary Falzon, April Matthews, Tammy Corica, Norman R Williams, Michael Baum
The Lancet Published Online June 5, 2010
"Partial breast irradiation: new standard for selected patients"
David Azria, Céline Bourgier
The Lancet, Early Online Publication, 5 June 2010
Written by Christian Nordqvist