Impact of Sequencing Radiation Therapy and Chemotherapy on Long-Term Local Toxicity for Early Breast Cancer: Results of a Randomized Study at 15-Year Follow-Up

Paola Pinnarò, Carolina Giordano, Alessia Farneti, Lidia Strigari, Valeria Landoni, Laura Marucci, Maria Grazia Petrongari, Giuseppe Sanguineti

Research output: Contribution to journalArticlepeer-review


PURPOSE: To compare long-term late local toxicity after either concomitant or sequential chemoradiation therapy after breast-conserving surgery.

METHODS AND MATERIALS: From 1997 to 2002, women aged 18 to 75 years who underwent breast-conserving surgery and axillary dissection for early breast cancer and in whom CMF (cyclophosphamide, methotrexate, and 5-fluorouracil) chemotherapy was planned were randomized between concomitant and sequential radiation therapy. Radiation therapy was delivered to the whole breast through tangential fields to 50 Gy in 20 fractions over a period of 4 weeks, followed by an electron boost. Surviving patients were tentatively contacted and examined between March and September 2014. Patients in whom progressive disease had developed or who had undergone further breast surgery were excluded. Local toxicity (fibrosis, telangiectasia, and breast atrophy or retraction) was scored blindly to the treatment received. A logistic regression was run to investigate the effect of treatment sequence after correction for several patient-, treatment-, and tumor-related covariates on selected endpoints. The median time to cross-sectional analysis was 15.7 years (range, 12.0-17.8 years).

RESULTS: Of 206 patients randomized, 154 (74.8%) were potentially eligible. Of these, 43 (27.9%) refused participation and 4 (2.6%) had been lost to follow-up, and for 5 (3.2%), we could not restore planning data; thus, the final number of analyzed patients was 102. No grade 4 toxicity had been observed, whereas the number of grade 3 toxicity events was low (<8%) for each item, allowing pooling of grade 2 and 3 events for further analysis. Treatment sequence (concomitant vs sequential) was an independent predictor of grade 2 or 3 fibrosis according to both the National Cancer Institute Common Terminology Criteria for Adverse Events (odds ratio [OR], 4.05; 95% confidence interval [CI], 1.34-12.2; P=.013) and the SOMA (Subjective, Objective, Management and Analytic) scale (OR, 3.75; 95% CI, 1.19-11.79; P=.018), as well as grade 2 or 3 breast atrophy or retraction (OR, 3.87; 95% CI, 1.42-10.56; P=.008). No effect on telangiectasia was detected.

CONCLUSIONS: At long-term follow-up, concomitant chemoradiation therapy has a detrimental effect on both fibrosis and retraction with an approximately 4-fold increase in the odds of grade 2 or 3 toxicity.

Original languageEnglish
Pages (from-to)1201-9
Number of pages9
JournalInternational Journal of Radiation Oncology Biology Physics
Issue number4
Publication statusPublished - Jul 15 2016


  • Journal Article


Dive into the research topics of 'Impact of Sequencing Radiation Therapy and Chemotherapy on Long-Term Local Toxicity for Early Breast Cancer: Results of a Randomized Study at 15-Year Follow-Up'. Together they form a unique fingerprint.

Cite this