Meeting NewsPerspective

Once-weekly, conventional breast radiotherapy yield similarly low long-term adverse effects

Women with early breast cancer who received once-weekly, hypofractionated radiotherapy exhibited low rates of normal tissue effects comparable to those of conventional radiation therapy at 10 years, according to study findings presented at American Society for Radiation Oncology Annual Meeting.

“This study says it’s possible to find a regimen that would allow early-stage breast cancer patients to be treated only once a week over 5 weeks rather than daily over the same time period,” Murray Brunt, MD, professor of clinical oncology at University Hospitals of North Midlands and Keele University in the U.K., said in a press release. “Findings should help doctors discuss risks and benefits with their patients for various courses of radiation therapy and inform shared decision-making between physicians and patients.”

In the U.K. FAST trial, researchers evaluated 915 women aged 50 years and older with invasive breast carcinoma (pT1-2 pN0) who were recruited from 18 centers in the U.K. between 2004 and 2007. Researchers randomly assigned patients 1:1:1 to one of three whole-breast radiotherapy schedules: 50 Gy in 25 fractions over 5 weeks, 30 Gy in five fractions over 5 weeks or 28.5 Gy in five fractions over 5 weeks.

Patients scheduled to undergo lymphatic/breast boost radiotherapy or neoadjuvant cytotoxic therapy were excluded from the analysis.

Clinicians assessed normal tissue effects (NTE) annually for 10 years, comparing photographs taken at 2 and 5 years with pre-radiotherapy baseline assessment.

The study’s composite endpoint was any clinician-evaluated NTE. Recurrence of breast tumors served as a secondary endpoint.
clinician-assessed breast NTE was significantly higher at 5 and 10 years for the 30 Gy group vs. the 50 Gy group ( P= .008), but the difference in late NTE effects between the 50 Gy group and the 28.5 Gy group was not statistically significant.

At both 5 and 10 years, there was a very low prevalence of marked NTE.

Compared with 50 Gy, excess of moderate/marked NTE among the 30 Gy group included: 10.5% (95% CI,4.9-16.1) at 5 years and +9.4% (95% CI, 1.1-17.6) at 10 years.

For 28.5 Gy, excess of moderate/marked effects were 2.4% (95% CI, -2.5-7.3) at 5 years and 5.5% (95% CI, -2.3-13.3) at 10 years.

A total of 10 local recurrences (three with 50 Gy and 30 Gy each, and four with 28.5 Gy) and 96 deaths (33 at 50 Gy, 33 at 30 Gy, and 30 at 28.5 Gy) were reported at 9.9 years’ follow-up.

“The profile of adverse effects to normal breast tissue was similar between the 28.5 Gy and 50 Gy groups, but rates were higher after 30 Gy given in five fractions over 5 weeks,” Brunt said in the press release. “This disparity is rooted in differences between the two regimens in fractionation sensitivity.”

The researchers are now investigating a radiotherapy course of five fractions over five consecutive days.

“A schedule like this would have significant clinical and practical implications, such as allowing radiation therapy to be integrated more closely with surgery and other therapies,” Brunt said.– by Jennifer Byrne

Reference:

Brunt M, et al. Abstract LBA2. Presented at: American Society for Radiation Oncology Annual Meeting; Oct. 21-24, 2018; San Antonio.

Disclosures : The authors report no relevant financial disclosures.

Women with early breast cancer who received once-weekly, hypofractionated radiotherapy exhibited low rates of normal tissue effects comparable to those of conventional radiation therapy at 10 years, according to study findings presented at American Society for Radiation Oncology Annual Meeting.

“This study says it’s possible to find a regimen that would allow early-stage breast cancer patients to be treated only once a week over 5 weeks rather than daily over the same time period,” Murray Brunt, MD, professor of clinical oncology at University Hospitals of North Midlands and Keele University in the U.K., said in a press release. “Findings should help doctors discuss risks and benefits with their patients for various courses of radiation therapy and inform shared decision-making between physicians and patients.”

In the U.K. FAST trial, researchers evaluated 915 women aged 50 years and older with invasive breast carcinoma (pT1-2 pN0) who were recruited from 18 centers in the U.K. between 2004 and 2007. Researchers randomly assigned patients 1:1:1 to one of three whole-breast radiotherapy schedules: 50 Gy in 25 fractions over 5 weeks, 30 Gy in five fractions over 5 weeks or 28.5 Gy in five fractions over 5 weeks.

Patients scheduled to undergo lymphatic/breast boost radiotherapy or neoadjuvant cytotoxic therapy were excluded from the analysis.

Clinicians assessed normal tissue effects (NTE) annually for 10 years, comparing photographs taken at 2 and 5 years with pre-radiotherapy baseline assessment.

The study’s composite endpoint was any clinician-evaluated NTE. Recurrence of breast tumors served as a secondary endpoint.
clinician-assessed breast NTE was significantly higher at 5 and 10 years for the 30 Gy group vs. the 50 Gy group ( P= .008), but the difference in late NTE effects between the 50 Gy group and the 28.5 Gy group was not statistically significant.

At both 5 and 10 years, there was a very low prevalence of marked NTE.

Compared with 50 Gy, excess of moderate/marked NTE among the 30 Gy group included: 10.5% (95% CI,4.9-16.1) at 5 years and +9.4% (95% CI, 1.1-17.6) at 10 years.

For 28.5 Gy, excess of moderate/marked effects were 2.4% (95% CI, -2.5-7.3) at 5 years and 5.5% (95% CI, -2.3-13.3) at 10 years.

A total of 10 local recurrences (three with 50 Gy and 30 Gy each, and four with 28.5 Gy) and 96 deaths (33 at 50 Gy, 33 at 30 Gy, and 30 at 28.5 Gy) were reported at 9.9 years’ follow-up.

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“The profile of adverse effects to normal breast tissue was similar between the 28.5 Gy and 50 Gy groups, but rates were higher after 30 Gy given in five fractions over 5 weeks,” Brunt said in the press release. “This disparity is rooted in differences between the two regimens in fractionation sensitivity.”

The researchers are now investigating a radiotherapy course of five fractions over five consecutive days.

“A schedule like this would have significant clinical and practical implications, such as allowing radiation therapy to be integrated more closely with surgery and other therapies,” Brunt said.– by Jennifer Byrne

Reference:

Brunt M, et al. Abstract LBA2. Presented at: American Society for Radiation Oncology Annual Meeting; Oct. 21-24, 2018; San Antonio.

Disclosures : The authors report no relevant financial disclosures.

    Perspective
    Rahul Tendulkar

    Rahul Tendulkar

    The FAST trial from the U.K. studied an unconventional radiation dose schedule by North American standards. The investigators tested radiation to the whole breast once weekly for 5 weeks using two different doses and determined that patients in the higher dose arm (30 Gy) had higher rates of late side effects such as breast shrinkage, hardness, seromas and telangiectasias. The lower weekly dose arm (28.5 Gy) had similar NTEs compared with the standard daily fractionation group (50 Gy in 25 treatments over 5 weeks), and all three arms had extremely low rates of tumor recurrence. While it is unlikely that such a once-weekly dosing schedule will be adopted in North America, the investigators are next studying whether five fractions of breast radiotherapy in 5 consecutive days will be safe and effective. With now a well-established role for hypofractionated radiation therapy in early stage breast cancer, further trials will help determine the optimal dose, timing and volume of breast tissue irradiated.

     

    • Rahul Tendulkar, MD
    • Cleveland Clinic.

    Disclosures: Tendulkar reports no relevant financial disclosures.

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