Impact of sequencing radiotherapy and chemotherapy on long-term local toxicity for early breast cancer: results of a randomized study at 15 year follow up
Mené sur 102 patientes atteintes d'un cancer du sein de stade précoce traité entre 1997 et 2002 (âge : 18 à 75 ans ; durée de suivi : 15 ans), cet essai compare, du point de vue de la toxicité locale à long terme, l'intérêt d'une chimioradiothérapie séquentielle et d'une chimioradiothérapie concomitante après un traitement conservateur
Purpose : To compare long-term late local toxicity after either concomitant (CONC) or sequential (SEQ) chemoradiotherapy after breast conserving surgery. Methods and Materials : From 1997 to 2002, women aged 18–75 years who had breast-conserving surgery and axillary dissection for early breast cancer and in whom CMF chemotherapy was planned were randomized between CONC or SEQ radiotherapy. Radiotherapy was delivered to the whole breast through tangential fields to 50 Gy/20 fractions/4 weeks, followed by an electron boost. Surviving patients were tentatively contacted and examined between March and September 2014. Patients who had developed progressive disease or had undergone further breast surgery were excluded. Local toxicity (fibrosis, telangiectasia, breast atrophy/retraction) was scored blindly to the treatment received. A logistic regression was run to investigate the effect of treatment sequence after correcting for several patient-, treatment- and tumor-related covariates on selected endpoints. The median time to cross sectional analysis is 15.7 years (range: 12.0-17.8 yrs). Results : Of 206 patients randomized, 154 (74.8%) were potentially eligible. Of them, 43 (27.9%) refused participation, 4 (2.6%) had been lost to follow up and for 5 (3.2%) we could not restore planning data, for a final number of 102 analyzed patients. No grade (GR) 4 toxicity had been observed, while the number of GR3 toxicity events was low (<8%) for each item, allowing pooling GR2 and 3 events for further analysis. Treatment sequence (CONC vs SEQ) was an independent predictor of GR2-3 fibrosis according to both CTCAE (OR: 4.05, 95%CI: 1.34-12.2, p=0.013) and SOMA (OR: 3.75, 95%CI: 1.19-11.79, p=0.018) as well as GR2-3 breast atrophy/retraction (OR: 3.87, 95%CI: 1.42-10.56, p=0.008). No effect was detected on telangiectasia. Conclusions : At long term follow up, concomitant chemoradiotherapy has a detrimental effect on both fibrosis and retraction with a ≈4-fold increase in the odds of GR2-3 toxicity.