1. Goodwin, Peter M.

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AMSTERDAM, Netherlands-Local recurrence rates were no higher among women with low-risk early breast cancer treated with radiotherapy to the breast tumor bed alone as compared with those receiving whole breast irradiation-while toxicity was lower in finings from the IMPORT LOW trial reported at the 2016 European Breast Cancer Conference (Abstract 4LBA).

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"This form of partial breast radiotherapy has equivalent control of the cancer but less side effects for patients," said lead investigator Charlotte E. Coles, PhD, from the Oncology Centre, Cambridge University Hospitals in Cambridge, U.K.


She described rates of local relapse as "very low" in all treatment groups, including those receiving less radiotherapy, and said there were few moderate or marked changes in normal breast tissue across all groups. She added partial breast irradiation was easy to deliver, shouldn't cost more money, and could even save money in some countries.


Intensity-Modulated Radiotherapy

The phase III IMPORT LOW study involved 2,018 women over 50 who had tumors of any grade up to a diameter of three centimeters with or without lymph node involvement. Around 90 percent of the participants were in their early 60s, had grade 1 or 2 tumors less than two centimeters in diameter, and were lymph node negative.


They were randomized into three groups to receive treatment with intensity-modulated radiotherapy (IMRT) according to three schedules. Women in the control arm had the UK standard whole breast radiotherapy: 40 Gray (Gy) of radiation in 15 fractions over three weeks. Patients in the first test arm received partial breast radiotherapy with 40 Gy to the tumor bed, while those in the second test arm had the same tumor-bed irradiation but also received 36 Gy to the rest of the breast.


The primary endpoint was local tumor control in the ipsilateral breast, with key secondary endpoints being late adverse effects measured by a combination of clinical and photographic criteria and patient self-assessments.


"The first thing to say was that we had very good follow-up," Coles told Oncology Times. The median follow-up period was 71 months and more than 90 percent of the patients completed five-year patient report forms.


"And we found that the local relapse rates were very low across all arms-around 1 percent-and [there was] no statistically significant difference between the arms," she said. Coles emphasized that since the study had met pre-defined criteria for non-inferiority, it showed that treatments in the partial and reduced-irradiation test arms were non-inferior in efficacy to whole breast radiotherapy.


Coles also thought toxicity was especially important because it is permanent and can cause both physical and psychological problems for the future. So the study looked at toxicity as recorded by patients and clinicians. "We found that toxicity was very low across all of the arms and this may be due to the fact that all patients received intensity modulated radiotherapy," she said.


She added that partial breast radiotherapy brought benefit in terms of factors reported by patients, such as changes in breast appearance and texture and by clinicians in their assessments of factors including shrinkage, induration, telangiectasia, and edema.


Looking beyond five years, Coles said that, because recurrences tend to increase linearly with time, she would expect-as in other studies-that at 10 years the rates would double across all arms. "So you'd still be looking at around a 2 percent local relapse rate-we think-at 10 years, but clearly we need to continue to follow these patients to confirm that," she said.


When she was asked about the possibility of withholding radiotherapy altogether, she said the challenge had been how to select patients for this, and that she was looking forward to seeing data from upcoming studies using biomarkers of relapse to identify patients with very low risk of recurrence.


But she was already bullish about bringing the findings from IMPORT LOW into practice. "We hope that the evidence of benefit we have shown in this trial will bring about a change in practice worldwide, and enable very many more women with early breast cancer to undergo this treatment," Coles said.


She added that, because breast cancer mortality rates were falling and more women were surviving their cancers, it was "particularly important to keep any treatment toxicity to the absolute minimum."


Low-Risk Breast Cancer

Emiel J.T. Rutgers, MD, PhD, a Surgical Oncologist and Head of Department at the Netherlands Cancer Institute, Amsterdam, told Oncology Times the findings from IMPORT LOW added to existing data showing that, in women with low-risk breast cancer, partial breast irradiation provides good local control and less toxicity.


Although some studies had found slightly higher rates of local relapse rates and complications such as fibrosis with partial breast radiotherapy, he thought the new data were significant. "This study is quite convincing that this type of partial breast irradiation does provide excellent local control at five years," he said. And he had no doubt this would continue out to 10 years-with limited morbidity. "To me, this should be taken on board in the decision-making of treatment of low risk breast cancer patients," he said.


Fatima Cardoso, MD, Director of the Breast Unit at Champalimaud Clinical Centre in Lisbon, Portugal, and Chair of the European Cancer Conference, said, "Overtreatment is a problem in cancers with a low risk of recurrence. This important study shows that, at least at five years follow-up, radiotherapy focused around the tumor bed with the IMRT technique provides as good local control as whole breast radiation and is associated with fewer side effects. This may, indeed, lead to a change in practice with benefits for patients and society, since it will also reduce costs. Longer follow-up is needed, however, since low-risk breast cancer has a long natural history."


Peter M. Goodwin is a contributing writer.