June 24, 2024


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Long-term APBI Cosmetic, Toxicity Data Reported

Long-term cosmetic and toxicity outcomes are good for both accelerated partial breast irradiation (APBI) delivered with 3D-conformal radiotherapy and whole-breast irradiation (WBI), with the latter having a slight edge, the IRMA trial shows.

Findings were reported at the European Society for Radiology and Oncology 2020 Online Congress by Bruno Meduri, MD, a radiation oncologist at University Hospital of Modena, Italy.

Uptake of APBI has increased since it was approved nearly 2 decades ago. However, its long-term outcomes are still being parsed, and issues such as appropriate patient selection and optimal delivery technique are still being clarified (Curr Breast Cancer Rep. 2020;18:1-10).

IRMA is a European, multicenter, phase 3 randomized controlled trial conducted among 3,279 women aged 49 years and older who underwent breast-conserving surgery for early-stage breast cancer (measuring <3 cm in diameter, and pathologic N0 or N1) with negative resection margins.

The women were randomized to APBI using 3D-conformal radiotherapy (38.5 Gy in 10 fractions, twice daily) or conventional or hypofractionated WBI (50.0 Gy in 25 fractions, once daily). All additionally received adjuvant therapy according to institutional guidelines.

Patients and physicians separately rated cosmetic outcomes on a 4-point scale using the untreated breast as a reference, and toxicity was graded with the Radiation Therapy Oncology Group (RTOG) scale.

Over a median follow-up of 5 years, patients rated cosmesis more favorably than physicians did at all time points, and there was a trend toward slight worsening of cosmesis in the APBI group with time, Meduri reported.

At 1 year, cosmesis did not differ significantly between treatment groups regardless of the rater. But compared with the WBI group, the APBI group more often had patient-rated fair to poor cosmesis at 3 years (12.7{f2a9790f1f5b326f5addd27543ef870bdef34be2bb42188b5ff1576c2dc9b21c} vs. 9.4{f2a9790f1f5b326f5addd27543ef870bdef34be2bb42188b5ff1576c2dc9b21c}; P =.02) and at 5 years (15.0{f2a9790f1f5b326f5addd27543ef870bdef34be2bb42188b5ff1576c2dc9b21c} vs. 10.1{f2a9790f1f5b326f5addd27543ef870bdef34be2bb42188b5ff1576c2dc9b21c}; P = .007), as well as physician-rated fair to poor cosmesis at 3 years (18.0{f2a9790f1f5b326f5addd27543ef870bdef34be2bb42188b5ff1576c2dc9b21c} vs. 13.1{f2a9790f1f5b326f5addd27543ef870bdef34be2bb42188b5ff1576c2dc9b21c}; P = .003) and at 5 years (18.4{f2a9790f1f5b326f5addd27543ef870bdef34be2bb42188b5ff1576c2dc9b21c} vs. 14.2{f2a9790f1f5b326f5addd27543ef870bdef34be2bb42188b5ff1576c2dc9b21c}; P = .04).

Women treated with APBI had less acute skin toxicity (P < .001), with 4.9{f2a9790f1f5b326f5addd27543ef870bdef34be2bb42188b5ff1576c2dc9b21c} developing grade 2 toxicity, compared with 21.4{f2a9790f1f5b326f5addd27543ef870bdef34be2bb42188b5ff1576c2dc9b21c} of peers treated with WBI. Late skin toxicity was also less common in the APBI group overall (P < .001), but the rate of grade 3 or 4 late skin toxicity was similar.

On the other hand, the APBI group had more late bone toxicity overall (P < .001) and late bone toxicity of grade 3 or 4 (1.0{f2a9790f1f5b326f5addd27543ef870bdef34be2bb42188b5ff1576c2dc9b21c} vs. 0{f2a9790f1f5b326f5addd27543ef870bdef34be2bb42188b5ff1576c2dc9b21c}; P < .05), as well as more late soft tissue (subcutaneous) toxicity overall (P < .001) and late soft tissue toxicity of grade 3 or 4 (2.6{f2a9790f1f5b326f5addd27543ef870bdef34be2bb42188b5ff1576c2dc9b21c} vs. 1.1{f2a9790f1f5b326f5addd27543ef870bdef34be2bb42188b5ff1576c2dc9b21c}; P < .05).

The two groups had essentially the same late lung toxicity.

Women treated with APBI had higher 5-year cumulative incidences of soft tissue toxicity of grade 2 or worse (29.7{f2a9790f1f5b326f5addd27543ef870bdef34be2bb42188b5ff1576c2dc9b21c} vs. 17.9{f2a9790f1f5b326f5addd27543ef870bdef34be2bb42188b5ff1576c2dc9b21c}; P < .0001) and grade 3 or worse (2.6{f2a9790f1f5b326f5addd27543ef870bdef34be2bb42188b5ff1576c2dc9b21c} vs. 1.1{f2a9790f1f5b326f5addd27543ef870bdef34be2bb42188b5ff1576c2dc9b21c}; P = .0016). Cumulative incidences of skin toxicity of these grades did not differ significantly.

Importantly, the prevalences of late soft tissue and skin toxicity at 5 years were much lower than the cumulative incidences, Meduri noted. “This means that the side effects in some patients tend to resolve over time.”

Although the prevalence of grade 2-4 skin toxicity increased slightly at 3 years and 5 years in both groups, the prevalence of grade 2-4 soft tissue toxicity was stable.

Finally, the volume that received at least 38.5 Gy of radiation was higher for patients who developed late grade 3 or 4 bone toxicity than for those who did not (2.1 vs. 0.82 cc; P = .027), whereas other dosimetric parameters were similar.

“The toxicity of the whole cohort was very low,” Meduri summarized. “APBI was associated with a slightly higher rate of late soft tissue and bone toxicity, with a slight decrease in cosmetic outcome at 5 years. But longer follow-up is needed to confirm these results.”

The IRMA findings confirm previous results from the RAPID trial showing that APBI delivered via 3D-conformal radiotherapy may be associated with increased rates of toxicity, Chirag Shah, MD, a radiation oncologist at the Cleveland Clinic in Ohio, said in an interview.

“While cancer control outcomes were not presented, the toxicity outcomes are important and validate why many are moving away from 3D-conformal radiotherapy APBI,” he elaborated. “We are seeing increased use of APBI in some centers in the U.S., though there has been a greater shift to IMRT [intensity-modulated radiation therapy] based on 10-year data from the Florence randomized trial, which showed reduced side effects.”

“I think the results of this study are practice-confirming,” Shah concluded. “Moving forward, shorter APBI schedules will be considered as we now have 5-fraction whole-breast regimens available, as assessed in the FAST and FAST-Forward trials.”

Meduri disclosed expert board service for MSD, and financial support for attending congresses from Ipsen, AstraZeneca, and Merck. The trial was sponsored by Regione Emilia-Romagna. Shah disclosed consulting for Impedimed and PreludeDX, and receiving grants from Varian, VisionRT, and PreludeDX.

SOURCE: Meduri B et al. ESTRO 2020. Abstract OC-0611.

This article originally appeared on MDedge.com, part of the Medscape Professional Network.