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Accelerated Radiation Therapies Move Forward in Early Breast Cancer


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Two studies reported at the 2021 American Society for Radiation Oncology (ASTRO) Annual Meeting provide evidence in support of the use of accelerated radiation therapies as safe alternatives to standard radiotherapy options following breast-conserving surgery.

Cameron Thorpe, MD

Cameron Thorpe, MD

Catheryn Yashar, MD, FABS, FACR, FASTRO

Catheryn Yashar, MD, FABS, FACR, FASTRO

The phase III MC1635 trial showed that extreme hypofractionated radiation therapy for localized breast cancer is as safe and well tolerated as moderate hypofractionation, according to lead author Cameron Thorpe, MD, of the Mayo Clinic, Phoenix.1 In the single-arm, phase II TRIUMPH-T trial, three-fraction accelerated partial-breast irradiation achieved effective disease control with low toxicity compared with historical data from studies of standard accelerated partial-breast irradiation, reported lead author Catheryn Yashar, MD, FABS, FACR, FASTRO, of the University of California, San Diego.2

MC1635 Trial

The phase III MC1635 trial enrolled 107 patients with localized breast cancer (T1–T3, N0–N1, M0) managed with breast-conserving surgery. They were randomly assigned 1:1 to whole-breast radiotherapy with moderate (40 Gy over 15 fractions) or extreme hypofractionation (25 Gy over 5 fractions).

The hypothesis was that extreme hypofractionated whole-breast radiotherapy would result in similar outcomes compared with moderately hypofractionated radiotherapy after lumpectomy in patients with early breast cancer.

Participants in the trial were 18 or older and underwent breast-conserving surgery. More than half (55%) had invasive ductal carcinoma; 20% had invasive lobular carcinoma; 16% had ductal carcinoma in situ; and 9% to 10% had mixed or other subtypes. Regarding tumor grade, 31% had grade 1 tumors, 41% had grade 2 tumors, and 28% had grade 3 tumors.

Patient characteristics were well balanced between the two arms. Most patients had node-negative disease and invasive carcinoma. Few patients received neoadjuvant therapy, most had sentinel lymph node biopsy, and the majority did not receive a radiation boost.

Dr. Thorpe reported on the results of an interim analysis of toxicity, quality of life, and cosmesis. At a median follow-up of 20 months, there were no grade 3 toxicities and little difference between the treatment arms in grade 2 toxicities, with four patients in each arm experiencing grade 2 toxicity. Grade 2 toxicities consisted mostly of radiation dermatitis in six patients and fibrosis and lymphedema in one patient each.

Patient-reported outcomes reflected that “mild” or worse skin burns were almost four times more common with moderate hypofractionation: 58.7% vs 27.9% (P = .004). Across several validated measures, quality-of-life scores showed no difference between arms at all time points measured.

Deterioration in cosmesis 3 months or more after radiotherapy was similar between treatment arms: 1.6% and 1.7%, respectively. The average Harvard cosmesis score was similar between arms at all timepoints. No cancer deaths or recurrences were reported in either arm.

“MC1635 suggests that extreme hypofractionation with 25 Gy in 5 fractions for early breast cancer is well tolerated compared with moderate hypofractionation, with similar quality of life and cosmesis between the arms,” Dr. Thorpe concluded. “Further follow-up is warranted, with a follow-up of just 20 months.”

TRIUMPH-T Trial

Investigators of the TRIUMPH-T trial sought to determine whether an ultra-short course of brachytherapy (22.5 Gy over 3 days given in 7.5 Gy fractions) could be a promising alternative to standard 5-day/10-fraction accelerated partial-breast irradiation in eligible patients following breast-conserving surgery. The investigators specifically looked at safety, 3-year local control rate, and cosmesis with the accelerated partial-breast irradiation technique.

The prospective, multi-institutional study enrolled 200 patients. Eligibility requirements included patient age of 45 or older, ductal carcinoma in situ or invasive breast carcinoma, and hormone receptor–positive tumors ≤ 3 cm (with negative margins and no metastases to axillary nodes).

In this trial, accelerated partial-breast irradiation was 7.50 Gy delivered in 3 fractions over 2 to 3 days with interstitial brachytherapy or a single-entry device (no external beam). A minimum of 6 hours between dose fractions was required. Treatment was begun within 1 to 5 days of the acquisition of the planning CT scan.

“This was enhanced convenience for patients, which may result in increased access to the adjuvant irradiation recommended as part of breast-conserving -therapy, which we know is underutilized,” she said.

The median patient age was 65. A total of 78.5% had invasive ductal carcinoma; 7% had invasive lobular carcinoma; and 14% had ductal carcinoma in situ. Negative margins were found in 100% with 8% of patients having margins < 2 mm. Hormonal therapy was received by 89%; chemotherapy, in 2.5%; and both, in 2.5%.

KEY POINTS

  • In the phase III MC1635 trial, extreme hypofractionation with 25 Gy in 5 fractions for early breast cancer was found to be safe and well tolerated compared with moderate hypofractionation, with similar quality of life and cosmesis between the arms.
  • In the single-arm, phase II TRIUMPH-T trial, three-fraction accelerated partial breast irradiation achieved effective disease control with low toxicity compared with historical data from studies of standard accelerated partial breast irradiation.

The primary endpoint of the study was to determine the serious toxicity rate with the shorter course of accelerated partial-breast irradiation, with serious toxicity defined as greater than grade 2. The treatment did not have a serious toxicity rate exceeding 10% at 2 years and therefore was not found to be unsafe.

At a median follow-up of 3.6 years, researchers found that the shorter course of brachytherapy achieved excellent or good cosmesis in 95% of patients as measured by the Harvard scale. Grade 1 or 2 fibrosis at the treatment site was observed in 32%, and grade 3 fibrosis was noted in 1.7%. No grade 4 toxicities were reported.

Regarding local tumor control, at 3.6 years, there were two ipsilateral local recurrences (1.1%), two nodal recurrences (1.1%), no distant recurrences, one contralateral breast cancer, and two lung malignancies.

“Ultra-short breast brachytherapy is feasible and has low toxicity, with good local tumor control. The TRIUMPH-T dose fractionation was calculated such that we expect the local tumor control rate to be similar to the 10-fraction option,” Dr. Yashar concluded. “We believe this is a good alternative to 5-day/10-fraction accelerated partial-breast irradiation in eligible patients.” 

DISCLOSURE: Dr. Thorpe and Dr. Yashar reported no conflicts of interest.

REFERENCES

1. Yashar CM, Khan AJ, Haffty Jr BG, et al: Three-fraction TRIUMPH-T brachytherapy for delivery of APBI offers effective disease control with minimal late toxicity. 2021 ASTRO Annual Meeting. Abstract 11. Presented October 28, 2021.

2. Thorpe CS, DeWees TA, Corbin KS, et al: MC1635: Randomized phase III trial of hypofractionated radiotherapy to the whole breast after breast conserving surgery. 2021 ASTRO Annual Meeting. Abstract 10. Presented October 28, 2021.


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Invited discussant Elizabeth Nichols, MD, of the University of Maryland, School of Medicine, Baltimore, commented on both the phase II TRIUMPH-T and the phase III MC1635 trials.

“There are multiple techniques in use for accelerated partial breast irradiation. Optimal dose ...

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