AMSTERDAM—Locoregional radiotherapy to the internal mammary and medial supraclavicular lymph nodes in women who had already been treated successfully for breast cancer with standard regimens—including surgery, radiotherapy, and, when needed, chemotherapy—was shown to extend long-term survival in a study reported here at the European Cancer Congress (Abstract 2, accessed via http://eccamsterdam2013.ecco-org.eu/Scientific-Programme/Abstract-search.aspx#?).
The Phase III EORTC Radiation Oncology and Breast Cancer Groups 22922-10925 study, which was voted Best Abstract, randomized 4,004 patients between 1996 and 2004 to receive either chest nodal irradiation or usual care. The patients, none of who had metastatic disease at entry, had either axillary node involvement or medially located primary tumors.
All patients had standard primary therapy—the majority of them receiving radiation to the tumor bed and, after mastectomy, to the chest wall. Few had axillary radiotherapy. Nearly all patients with positive nodes, and two thirds of those without, had systemic therapy.
Those receiving the additional chest node irradiation had significant reductions in their risk of dying. The 10-year overall survival rate was raised by about two percent: from 80.7 to 82.3 percent; and at 10.9 years of follow-up, 382 patients had died in the nodal-irradiation group vs. 429 of the control patients.
Disease-free survival was increased from about 69 to 72 percent; and metastasis-free survival was improved from about 75 to 78 percent, with the benefits related neither to the number of nodes involved, nor to the stage of the disease.
Speaking at a news briefing, Philip Poortmans, MD, PhD, a radiation oncologist at Institute Verbeeten in Tilburg, Netherlands, who presented the data, explained that the fact that this benefit occurred across the board indicated that systemic and locoregional treatments were working together positively and were not in competition.
In both groups of patients, the causes of death were similar other than for breast cancer: 259 deaths were in the group receiving radiation to the chest nodes and 310 in the control group.
In an interview, he noted that up until now most oncologists have paid less attention to the chest lymph nodes in comparison to those in the axilla, partly because they are less accessible and also through fear of overtreatment. But the study findings were reassuring, he said. “We found that the chance of metastasis decreased by irradiating those lymph nodes by, at 10 years, three percent. And this led, as a second-level effect, to a decrease of death due to breast cancer.”
The results highlight the importance of optimal locoregional control in patients with breast cancer—that effectively treating the lymph nodes can stop the metastases at their source, preventing further spread, he said.
“The results of our trial contradict the existence of a ‘competition’ between locoregional and systemic treatments. Because there is an interaction between these treatments, in many patients their combination will result in an enhancement of the combined benefits—in other words, one plus one can equal more than two.”
Implications for Practice
“I would highly recommend the re-introduction of irradiation of the lymph nodes around the collar bone and behind the breast bone in patients who have either involved axillary lymph nodes or a tumor that is located centrally or internally located in the breast,” Poortmans continued.
Asked for his opinion for this article, John Yarnold, MBBS, MRCP, FRCR, Professor of Clinical Oncology at the Institute of Cancer Research in London, said, “We've been waiting 20 years for these data and we're delighted to see that there are positive gains to be had.” The lymph nodes are relatively “hidden” behind the breast bone, but it is now clear that they are a very important area of focus, he added.
Professor Ian Kunkler, MRCP, FRCR, FRCPE, FRSM, Consultant in Clinical Oncology at Edinburgh Cancer Centre in Scotland, said he was surprised by the results: “We've known for many years that the internal mammary nodes can be involved, but actually, the clinical recurrence rates are very low.”
The finding that additional radiotherapy to the chest nodes confers a benefit of both disease-free and overall survival is clinically significant, he said, and the lack of any significant increase in cardiac mortality shows that this treatment, with modern three-dimensional treatment planning, can be given safely.
Yarnold said that although a two percent increase in overall survival might sound modest, this is in addition to the big gains in survival brought by other recent improvements in therapy for breast cancer, and is a welcome achievement.
Kunkler agreed: “Any benefit on the order of two to three percent—although it might sound small—in terms of benefit to patients is a very significant change.”
Poortmans said that the additional three percent increase in disease-free survival at 10 years could be tantamount to cure: “This means that if at 10 years you still have no metastasis or recurrence, that the risk is negligible. Many of those patients will therefore never recur and will be cured.”
Cornelis van de Velde, MD, PhD, President of the European CanCer Organisation and Professor of Surgery at Leiden University in the Netherlands, said he saw the findings as further advances in personalized therapy, “reaching the delicate balance between under-treatment leading to more recurrences and overtreatment resulting in toxicities: In past studies, radiotherapy as an adjunct to surgery has shown important improvements in locoregional control as well as survival, and these further survival benefits, without an increase in short- and long-term toxicities, are a valuable development.”
Audio Journal of Oncology with Oncology Times
Hear more about the reactions to this study on the iPad edition of this issue, with audio and video interviews conducted at the Congress with Philip Poortmans, Ian Kunkler, and John Yarnold, speaking to reporters Peter Goodwin and Sarah Maxwell.
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