GLASGOW, SCOTLAND-The policy of giving chest lymph node irradiation, in addition to whole-breast or chest-wall radiotherapy, to all women with axillary node-positive breast cancer after surgery was given strong encouragement here at the European Breast Cancer Conference.
Three large studies-presented at a workshop on regional control-reached the same overall conclusion, including a first report from Denmark.
In an interview, Philip Poortmans, MD, PhD, President of the European Society for Radiotherapy & Oncology (ESTRO), said, "Overall, the results are all pointing in the same direction, that optimization of local regional treatment decreases the risk of subsequent distant metastasis and thereby improves overall survival in breast cancer patients."
Poortmans, of Institute Verbeeten in the Netherlands, presented updated results from his group's EORTC ROG and BCG Phase III 22922/10925 trial confirming the benefits of additional irradiation to the internal mammary and medial supraclavicular lymph nodes for all patients with early breast cancer who had centrally or medially located tumors or one or more involved axillary nodes, including those receiving systemic therapy (Abstract 6).
That study of 4,004 patients treated at 46 institutions in 13 countries between 1996 and 2004 showed a survival benefit from the use of radiation therapy irrespective of the overall mix of treatment. At a median follow-up of more than 10 years, postoperative radiation increased overall, disease-free, and distant metastasis-free survival in patients with stages I-III breast cancer without any increase in non-breast cancer related mortality.
In the Danish study, adjuvant regional radiotherapy to the internal mammary nodes was shown to extend survival, the researchers said, in the as yet unpublished updated Danish DBCG-IMN nationwide 3,000-patient cohort study. (Less mature results were subsequently presented at ESTRO 33 last month-Abstract OC-0148).
After nine years of follow-up, 437 deaths were reported among patients who did not receive additional chest radiotherapy as compared with 359 deaths in women who did have radiotherapy-a reduction in 4.4 percent, with both groups also receiving systemic therapy.
Lise Bech Jellesmark Thorsen, MD, a PhD student in the Department of Experimental Clinical Oncology at Aarhus University Hospital in Denmark, explained that patients had been allocated to receive internal mammary node radiotherapy only if the right breast had been affected, since at the time of randomization the potential cardiotoxic effects of chest radiotherapy were considered to contraindicate its use among women with left-sided breast cancer.
In addition, subgroup analysis revealed a greater proportional benefit in women who had more systemic therapy: "The more intensive the systemic therapy, the better the effect of internal mammary node radiotherapy," she said. There was also a two percent reduction of breast cancer-specific deaths among the patients receiving radiation therapy-308 deaths in the radiotherapy group versus 366 among the remaining patients.
Timothy Whelan, MD, Professor at McMaster University in the Division of Radiation Oncology and Director of the Supportive Cancer Care Research Unit, discussed the involvement with the ongoing NCIC-CTG MA.20 Intergroup trial of regional nodal radiation in early breast cancer among patients with positive axillary lymph nodes undergoing breast-conserving surgery treated with chemotherapy or hormonal therapy.
The initial results (reported at the 2011 ASCO Annual Meeting-Abstract LBA1003) showed that regional nodal irradiation was associated with a decrease in isolated locoregional recurrence and a bigger decrease in distant metastasis. Whelan suggested that radiotherapy might be impeding regional nodal metastatic spread that had not been addressed fully by chemotherapy. As in the EORTC and Danish studies, there was a benefit in all women with node-positive disease, not only those with more than three positive nodes.
Poortmans said that while the data clearly demonstrated the value of such extra radiotherapy, there is a need for a multimodal approach. "We are in a multidisciplinary world, where an optimal combination of locoregional treatment-surgery, radiation therapy, systemic therapy-will give the best results."
Guideline Changes Soon?
John Yarnold, MBBS, MRCP, Professor of Clinical Oncology at the Institute of Cancer Research of Royal Marsden Hospital in London, who chaired the workshop, said he regarded the four percent improvement in overall survival reported from the Danish study along with the findings from the other two studies as potentially leading to a revision in the guidelines. He predicted that pending peer review of the latest data, he considered it inevitable that additional chest radiation directed to lymphatic channels would be adopted as standard in all women with node-positive disease, with some discussion still to be conducted concerning those with micrometastatic spread in a single node.