Incorporating New ASTRO Partial Breast Irradiation Guidelines Into Practice

Jennifer R. Bellon, MD, FASTRO, noted that further investigation is needed for various underrepresented subgroups. For example, clinicians should consider if a patient has lobular history and confirm with an MRI, and assess whether a patient has lymphovascular invasion.

Partial breast irradiation (PBI) may be an appropriate treatment for patients with early-stage breast cancer, although additional investigations may be needed for underrepresented subgroups in this population, according to a presentation at the 41st Annual Miami Breast Cancer Conference^® hosted by Physician’s Education Resource^® (PER^®).¹

The American Society for Radiation Oncology worked in conjunction with the American Society of Clinical Oncology and the Society of Surgical Oncology to develop clinical practice guidelines to determine if PBI could occur for patients with early-stage invasive breast cancer or ductal carcinoma in situ.² These guidelines asked 4 essential questions to determine when treatment should occur:

• What are the appropriate indications for PBI as an alternative to whole breast irradiation (WBI)?
• What are the appropriate PBI techniques with respect to ipsilateral breast recurrence outcomes?
• What are the appropriate dose-fractionation regimens?
• What are the appropriate PBI techniques with respect to toxicity and cosmesis?

Each question was followed by a series of recommendations, with factors determining whether the recommendation was strong and if there was a high quality of evidence. For question 1, there were 3 areas of controversy including patient age, tumor size, and adjuvant radiation therapy options.

Presenting author Jennifer R. Bellon, MD, FASTRO, director of Breast Radiation Oncology at Dana-Farber Cancer Institute and associate professor of Radiation Oncology at Harvard Medical School, noted there were several mature PBI trials that helped play a role in determining the consensus guidelines.

IMPORT LOW

The IMPORT LOW trial was a randomized study conducted in the United Kingdom.³ In the trial, patients were 50 years old or older, had tumors of less than 3 cm, and had 0 to 3 axillary lymph nodes. In the control arm (n = 674), WBI was given at 40 Gy in 15 fractions. The reduced dose arm (n = 673) had WBI given at 36 Gy in 15 fractions, and the PBI arm (n = 669) was given 40 Gy in 15 fractions only on the tumor bed.

The risk of local recurrence at 5 years was 1.1% with WBI, 0.2% for the reduced dose (HR, 0.33; 95% CI, 0.09-1.20; P value for WBI vs reduced dose = 0.003);for PBI, it was 0.5% (HR, 0.65; 95% CI, 0.23-1.84; P value for WBI vs PBI = 0.016).

The 5-year cumulative rate for breast appearance change was 47.7% (95% CI, 41.1%-54.8%; HR, 1) for WBI, 36.7% (95% CI, 30.6%-43.6%; HR, 0.74; 95% CI, 0.54-1.00; P = .051) for the reduced dose, and 35.1% (95% CI, 28.7%-42.5%; HR, 0.64; 95% CI, 0.46-0.89; P = .007) for PBI. Additional categories, which included the breasts becoming smaller, harder or firmer; shoulder stiffness; and skin appearance change demonstrated no significant variance between these subgroups.

Danish Breast Cancer Group Study

A phase 2 trial (NCT00892814) analyzed PBI vs WBI for elderly patients who underwent surgery for early breast cancer.⁴ A total of 865 patients were enrolled, with 434 assigned to receive WBI and 431 assigned to PBI. Patients who were older than 60, had T1N0 disease, and had estrogen receptor–positive, grade 1/2 non-lobular breast cancer were eligible for the study. Both treatment arms were given 40 Gy in 15 fractions.

The induration of grade 2/3 cumulative incidence was 3.5 years (HR, 0.50; 95% CI, 0.29-0.86). For WBI, it was 9.7% (95% CI, 7.0%-12.9%), and for PBI, it was 5.1% (95% CI, 3.2%-7.6%). The risk difference was –4.6% (95% CI, –8.2% to –0.9%). Additionally, induration by breast size and treatment volume were evaluated for large (13% vs 6%) and small subgroups (6% vs 5%).

Local regional recurrence by cumulative incidence was assessed at 5 and 9 years (HR, 1.75; 95% CI, 0.64-4.77). For WBI, it was 0.7% (95% CI, 0.2%-1.9%) and 1.7% (95% CI, 0.7%-3.6%) at 5 and 9 years, respectively, and the rates were 1.2% (95% CI, 0.4%-2.6%) and 3.1% (95% CI, 1.5%-5.6%) for PBI. The risk difference was 0.5% (95% CI, –0.8% to 1.7%; P = .47) at 5 years and 1.4% at 9 years (95% CI, –1.1% to 3.8%; P = .30).

RAPID Trial

The RAPID trial (NCT00282035) was conducted across Canada, Australia, and New Zealand.⁵ Patients were randomly assigned 1:1 to receive external beam accelerated PBI at 38.5 Gy in 10 fractions given twice a day on days 5 to 8 or WBI given at 42.5 Gy in 16 fractions given once per day over 21 days or 50 Gy in 25 fractions once per day over 35 days.

The 5-year event rate for the accelerated PBI arm was 2.3% and 3.0% at 8 years; these rates were 1.7% and 2.8% for WBI (HR, 1.27; 90% CI, 0.84-1.91). Acute toxicity occurred in 28.0% of patients who received accelerated PBI vs 45.4% with WBI, and late toxicity occurred in 32.3% vs 13.3%.

NSABP-39/RTOG 0413 Study

A phase 3 trial (NCT00103181) assessed WBI at 50 Gy as 2.0 Gy per fraction or 50.4 Gy as 1.8 Gy per fraction to whole breast followed by an optional boost of 60 Gy or more, or PBI at 10 fractions each day for 5 to 8 days, 34 Gy in 3.4 Gy fractions, or 38.5 Gy in 3.85 Gy fractions.⁶ The trial aimed to look at the effect of accelerated PBI after breast-conserving surgery. A total of 2109 patients were assigned to the WBI group vs 2107 in the accelerated PBI group.

A majority of patients in the WBI and PBI arms, respectively, were between 50 and 70 years old (50% vs 49%) followed by less than 50 years (38% vs 38%). Most patients were White (89% vs 90%), non-Hispanic (91% vs 91%), and postmenopausal (61% vs 61%).

The 10-year ipsilateral breast tumor recurrence (IBTR) rate was 4.6% in the accelerated PBI group vs 3.9% in the WBI group. Adverse effect (AE) data were available for 97% of patients. Grade 3 AEs occurred in 10% of patients in the PBI group vs 7% in the WBI group, and grade 4/5 toxicity occurred in less than 1% each.

University of Florence Study

A phase 3 trial (NCT02104895) assessed 520 patients who were given external-beam accelerated PBI intensity-modulated radiation therapy.⁷ All enrolled patients were older than 40 and had a tumor size less than 2.5 cm. Patients were treated with either 6 Gy in 5 fractions every other day or 2 Gy in 25 fractions plus a 10 Gy boost. The median follow-up was 10.7 years.

The 10-year IBRT rate was 3.7% in the accelerated PBI group vs 2.5% in the WBI group (HR, 1.56; 95% CI, 0.55-4.37; P = .40). The physician-rated cosmesis between arms was 94.7% vs 72.7% (P = .0001) for excellent, 5.3% vs 25.4% for good, 0.0% vs 1.9% for fair, and 0.0% vs 0.0% for poor. The patient-rated cosmesis was 17.9% vs 5.1% (P = .0001) for excellent, 81.3% vs 80.3% for good, 0.8% vs 14.6% for fair, and 0.0% vs 0.0% for poor.

Concluding Thoughts

Bellon noted that further investigation is needed for various underrepresented subgroups. Clinicians should consider if a patient has lobular history and confirm with an MRI, and assess whether a patient has lymphovascular invasion. Additionally, trials should be created for those who have positive lymph nodes or a genetic predisposition to breast cancer and those who are under 40 years old, undergoing oncoplastic tissue rearrangement, or are not undergoing the surgical evaluation of the axilla.

References

1. Bellon JR. The new partial breast irradiation guidelines. Presented at the 41st Annual Miami Breast Cancer Conference hosted by Physician’s Education Resource; Miami, FL, March 7-10, 2024.
2. Shaitelman SF, Anderson BM, Arthur DW, et al. Partial breast irradiation for patients with early-stage invasive breast cancer or ductal carcinoma in situ: an ASTRO clinical practice guideline. Pract Radiat Oncol. 2024;14(2):112-132. doi:10.1016/j.prro.2023.11.001
3. Coles CE, Griffin CL, Kirby AM, et al. Partial-breast radiotherapy after breast conservation surgery for patients with early breast cancer (UK IMPORT LOW trial): 5-year results from a multicentre, randomised, controlled, phase 3, non-inferiority trial. Lancet. 2017;390(10099):1048-1060. doi:10.1016/S0140-6736(17)31145-5
4. Offersen BV, Alsner J, Nielsen HM, et al. Partial breast irradiation versus whole breast irradiation for early breast cancer patients in a randomized phase III trial: The Danish Breast Cancer Group partial breast irradiation trial. J Clin Oncol. 2022;40(36):4189-4197. doi:10.1200/JCO.22.00451
5. Whelan TJ, Julian JA, Berrang TS, et al. External beam accelerated partial breast irradiation versus whole breast irradiation after breast conserving surgery in women with ductal carcinoma in situ and node-negative breast cancer (RAPID): a randomised controlled trial. Lancet. 2019;394(10215):2165-2172. doi:10.1016/S0140-6736(19)32515-2
6. Vicini FA, Cecchini RS, White JR, et al. Long-term primary results of accelerated partial breast irradiation after breast-conserving surgery for early-stage breast cancer: a randomised, phase 3, equivalence trial. Lancet. 2019;394(10215):2155-2164. doi:10.1016/S0140-6736(19)32514-0
7. Meattini I, Marrazzo L, Saieva C, et al. Accelerated partial-breast irradiation compared with whole-breast irradiation for early breast cancer: long-term results of the randomized phase III APBI-IMRT-Florence Trial. J Clin Oncol. 2020;38(35):4175-4183. doi:10.1200/JCO.20.00650