Messaggi chiave
- L’uso di regimi ipofrazionati (HF) nella radioterapia post mastectomia (PMRT) è associato a un miglioramento della qualità della vita rispetto ai regimi con frazionamento tradizionale (CF), senza compromissione dell’efficacia. Tuttavia, i suoi esiti in pazienti sottoposte a ricostruzione con impianto dopo la chirurgia primaria non sono stati esaminati in modo prospettico. Per colmare tale lacuna, è stato condotto uno studio randomizzato di confronto tra PMRT HF vs CF in 400 pazienti candidate a RT adiuvante dopo mastectomia e ricostruzione immediata.
- Dallo studio non sono emerse differenze statisticamente significative tra i due gruppi in termini di miglioramento del benessere fisico (PWB) a 6 mesi, l’outcome primario. Tuttavia, l’interazione tra fascia di età e braccio dello studio è risultata significativa, con punteggi PWB a 6 mesi migliori nelle pazienti di età <45 anni trattate con regimi HF rispetto a CF (23,6 [IC 95%, 22,7-24,6] vs 22,0 [IC 95%, 20,7-23,3]; p = 0,047), nonché un minor grado di disturbo legato all’insorgenza di effetti avversi o nausea.
- Effetti tossici sulla parete toracica si sono verificati in 39 pazienti, senza differenze tra i due bracci, a una mediana di 7,2 mesi. L’analisi multivariata non ha evidenziato alcuna associazione tra la modalità di frazionamento e il rischio di tali effetti (braccio HF: hazard ratio, 1,02; p = 0,95). Meno pazienti nel braccio HF hanno dovuto sospendere temporaneamente il trattamento (2,7 vs 7,7%; p = 0,03) o assentarsi dal lavoro per malattia (8,5 vs 16,9%; p = 0,02). Nel complesso, questi dati sono utili a integrare le conoscenze attualmente disponibili sulla PMRT HF in pazienti sottoposte a mastectomia e successiva ricostruzione protesica.
Abstract
Importance
- Postmastectomy radiation therapy (PMRT) improves local-regional disease control and patient survival.
- Hypofractionation (HF) regimens have comparable efficacy and complication rates with improved quality of life compared with conventional fractionation (CF) schedules.
- However, the use of HF after mastectomy in patients undergoing breast reconstruction has not been prospectively examined.
Objective
- To compare HF and CF PMRT outcomes after implant-based reconstruction.
Design, setting, and participants
- This randomized clinical trial assessed patients 18 years or older undergoing mastectomy and immediate expander or implant reconstruction for breast cancer (Tis, TX, or T1-3) and unilateral PMRT from March 8, 2018, to November 3, 2021 (median [range] follow-up, 40.4 [15.4-63.0] months), at 16 US cancer centers or hospitals.
- Analyses were conducted between September and December 2023.
Interventions
- Patients were randomized 1:1 to HF or CF PMRT.
- Chest wall doses were 4256 cGy for 16 fractions for HF and 5000 cGy for 25 fractions for CF.
- Chest wall toxic effects were defined as a grade 3 or higher adverse event.
Main outcomes and measures
- The primary outcome was the change in physical well-being (PWB) domain of the Functional Assessment of Cancer Therapy-Breast (FACT-B) quality-of-life assessment tool at 6 months after starting PMRT, controlling for age.
- Secondary outcomes included toxic effects and cancer recurrence.
Results
- Of 400 women (201 in the CF arm and 199 in the HF arm; median [range] age, 47 [23-79] years), 330 patients had PWB scores at baseline and at 6 months.
- There was no difference in the change in PWB between the study arms (estimate, 0.13; 95% CI, -0.86 to 1.11; p = 0.80), but there was a significant interaction between age group and study arm (p = 0.03 for interaction).
- Patients younger than 45 years had higher 6-month absolute PWB scores if treated with HF rather than CF regimens (23.6 [95% CI, 22.7-24.6] vs 22.0 [95% CI, 20.7-23.3]; p = 0.047) and reported being less bothered by adverse effects (mean [SD], 3.0 [0.9] in the HF arm and 2.6 [1.2] in the CF arm; p = 0.02) or nausea (mean [SD], 3.8 [0.4] in the HF arm and 3.6 [0.8] in the CF arm; p = 0.04).
- In the as-treated cohort, there were 23 distant (11 in the HF arm and 12 in the CF arm) and 2 local-regional (1 in the HF arm and 1 in the CF arm) recurrences.
- Chest wall toxic effects occurred in 39 patients (20 in the HF arm and 19 in the CF arm) at a median (IQR) of 7.2 (1.8-12.9) months.
- Fractionation was not associated with chest wall toxic effects on multivariate analysis (HF arm: hazard ratio, 1.02; 95% CI, 0.52-2.00; p = 0.95).
- Fewer patients undergoing HF vs CF regimens had a treatment break (5 [2.7%] vs 15 [7.7%]; p = 0.03) or required unpaid time off from work (17 [8.5%] vs 34 [16.9%]; p = 0.02).
Conclusions and relevance
- In this randomized clinical trial, the HF regimen did not significantly improve change in PWB compared with the CF regimen.
- These data add to the increasing experience with HF PMRT in patients with implant-based reconstruction.