Women with early-stage breast cancer treated with lumpectomy followed by radiation therapy rated the cosmetic results for whole-breast and partial-breast irradiation to be equivalent, according to a new analysis of results from the phase III NRG Oncology/NSABP B39-RTOG 0413 clinical trial. Results from the new analysis were presented at the 2019 American Society for Radiation Oncology (ASTRO) Annual Meeting in Chicago.1
Previously reported results from the 0413 trial found that “post-lumpectomy partial-breast irradiation was not statistically equivalent to whole-breast irradiation,” the researchers conducting the new analysis noted. “However, with an absolute difference for in-breast recurrence at 10 years of less than 1%, it may be a reasonable option for many patients with breast cancer. The cosmetic outcome of partial-breast irradiation compared with whole-breast irradiation could be an important determinant for radiation method selection.”
Julia Wong, MD
Although the “oncologic results did not meet the criteria for equivalence as defined by the trial, it bears noting that the ipsilateral breast tumor recurrence rates were exceedingly low in both arms of the trial,” commented Julia Wong, MD, of the Dana-Farber Cancer Center, Boston, who served as discussant for the ASTRO science highlights session on breast cancer. “I think we should all agree that this is not a reason to rule out partial-breast irradiation. There are excellent local control rates with respect to either group.”
Equal Ratings From Women
A quality-of-life substudy to the 0413 trial was reported at this year’s ASCO Annual Meeting. The investigators concluded that at 36 months, partial-breast irradiation was more convenient and less fatiguing than whole-breast irradiation in patients not receiving chemotherapy. Cosmesis was slightly poorer, but it was equivalent to whole-breast irradiation in patients receiving chemotherapy.2
The cosmetic outcome study reported at ASTRO included separate analyses of 420 women treated with chemotherapy and 480 who did not receive chemotherapy. Cosmetic outcomes were assessed by three different methods: patient-rated global cosmetic score and satisfaction; global cosmetic score rating by physicians at the accruing site; and digital photos of the breasts taken at baseline, and 1 and 3 years after radiotherapy, scored by physicians blinded to the treatment, breast treated, chemotherapy use, and time point.
“At 36 months, there was no difference, according to the patient, with respect to whole-breast or partial-breast irradiation for global cosmetic score,” Dr. Wong said. “In contrast, the site-physician evaluation at 36 months modestly favored whole-breast over partial-breast irradiation.”
Digital-photo review also found no difference in cosmetic outcome between whole-breast and partial-breast radiation at 1 and 3 years. There were, however, differences in these ratings based on whether or not patients received chemotherapy. Cosmetic outcomes were rated slightly worse among patients who received partial-breast irradiation and chemotherapy, and among patients who received whole-breast irradiation, but not chemotherapy.
Patient-rated outcomes of excellent or good aligned with the site-physician rating 89% of the time and with the digital-photo review 85% of the time. In contrast, patient-rated outcomes of fair or poor aligned with the site-physician rating 45% of the time and with the digital-photo review 32% of the time.
Patient Satisfaction ‘Exceedingly High’
“It is important to note that patient satisfaction was exceedingly high for treatment and cosmetic outcomes,” Dr. Wong added. At 36 months, 86% of patients who had whole-breast irradiation and 81% of patients who had partial-breast irradiation expressed total satisfaction with their results. Less than 1% of patients who had whole-breast or partial-breast irradiation said they were totally dissatisfied.
Reviewing the results, Dr. Wong offered these comments: “This was a meticulous evaluation of cosmesis” with “reassuring results in light of the prior data from the RAPID trial, which showed worse outcomes with partial-breast irradiation at 3 and 5 years.3 Of course, the big question is why the difference between the RAPID trial and this trial. It is really not clear. There may be some subtle differences in radiation technique or volumes or subtleties in treatment delivery. We look forward to further analysis to be able to sort that out a little better.”
Concurrent Radiation and Cisplatin
Among the other studies chosen to be highlighted at the scientific session on breast cancer was a phase Ib trial to assess safety and toxicity and establish the maximum tolerated dose of concurrent cisplatin with adjuvant radiotherapy for women with stage II and II triple-negative breast cancer.4 As the study authors from Brigham and Women’s Hospital/Dana-Farber Cancer Institute noted, cisplatin “is an effective systemic chemotherapy in triple-negative breast cancer and is also a radiation sensitizer.”
The 55 study participants had either mastectomy or breast conservation therapy and could have had any prior preoperative or adjuvant therapy except cisplatin or carboplatin. Cisplatin was initiated at 10 mg/m2 intravenously once weekly and then escalated by 10 mg/m2 until a dose of 40 mg/m2 or maximum tolerated dose was reached. Radiation was delivered with conventional once-daily fractionation to the breast or chest wall, followed by a lumpectomy site “cone down” or incision boost at the discretion of the radiation oncologist. Radiation to the regional nodes was also at the discretion of the treating physician.
A maximum tolerated dose of 30 mg/m2 was established for patients who had mastectomy and 40 mg/m2 for patients who had breast conservation therapy. The most common adverse events within both groups were dermatitis (45% grade 2, 2% grade 3), leukopenia (15% grade 2, 15% grade 3), and fatigue (15% grade 2). Cisplatin was held or discontinued in 13 patients. The 3-year disease-free follow-up was 71% among those treated with breast conservation and 70% among those treated with -mastectomy.
Integrating Data and Asking Questions
“These are encouraging results, showing good tolerability,” Dr. Wong commented. “These oncologic outcomes are reasonable for 3 years, but these patient numbers are small, and we anticipate there will be more efficacy data with mature follow-up.”
Dr. Wong asked additional questions: “How do we integrate these and other data in terms of how to think about giving additional treatment for triple-negative disease or disease where we think the risk is higher? It is difficult to know when there are so many agents available. How do we not only choose them, but sequence them as well? We know that with the results from the CREATE-X trial, capecitabine is being used much more frequently.5 Should we be giving radiation concurrently or sequentially? What should we do about PARP [poly (ADP-ribose) polymerase] inhibitors? What about immunotherapy?”
Dr. Wong concluded with some thoughts on future therapeutic strategies. “We are moving toward tailoring additional systemic therapy for patients who had suboptimal responses to neoadjuvant chemotherapy. It remains to be seen how we work in these various agents as we get more and more data.” ■
DISCLOSURE: Dr. Wong reported no conflicts of interest.
1. White JR, Winter K, Cecchini RS, et al: Cosmetic outcome from post lumpectomy whole breast irradiation vs partial breast irradiation on the NRG Oncology/NSABP B39-RTOG 0413 phase III clinical trial. 2019 ASTRO Annual Meeting. Abstract 5. Presented September 16, 2019.
2. Ganz PA, Cecchini RS, White JR, et al: Patient-reported outcomes in NRG oncology/NSABP B-39/RTOG 0413: A randomized phase III study of conventional whole breast irradiation versus partial breast irradiation in stage 0, I, or II breast cancer. 2019 ASCO Annual Meeting. Abstract 508. Presented June 3, 2019.
3. Whelan T, Julian J, Levine, et al: RAPID: A randomized trial of accelerated partial breast irradiation using 3-dimensional conformal radiotherapy (3D-CRT). Cancer Research 79(4 suppl), 2019.
4. Bellon JR, Chen YH, Rees R, et al: A prospective phase I trial of concurrent cisplatin and radiation therapy in women with stage II and III triple-negative breast cancer. 2019 ASTRO Annual Meeting. Abstract 87. Presented September 16, 2019.
5. Masuda N, Lee SJ, Ohtani S, et al: Adjuvant capecitabine for breast cancer after preoperative chemotherapy. N Engl J Med 376:2147-2159, 2017.