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 journalArticle

Abstract

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
Volume95
Issue number4
DOIs
Publication statusPublished - Jul 15 2016

Fingerprint

sequencing
chemotherapy
breast
toxicity
radiation therapy
Radiotherapy
cancer
grade
Breast Neoplasms
Drug Therapy
fibrosis
Breast
Telangiectasis
surgery
Fibrosis
Segmental Mastectomy
atrophy
Odds Ratio
confidence
Confidence Intervals

Keywords

  • Journal Article

Cite this

@article{be54a6951a04460a9c008f6c2a326f43,
title = "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",
abstract = "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.",
keywords = "Journal Article",
author = "Paola Pinnar{\`o} and Carolina Giordano and Alessia Farneti and Lidia Strigari and Valeria Landoni and Laura Marucci and Petrongari, {Maria Grazia} and Giuseppe Sanguineti",
note = "Copyright {\circledC} 2016 Elsevier Inc. All rights reserved.",
year = "2016",
month = "7",
day = "15",
doi = "10.1016/j.ijrobp.2016.03.016",
language = "English",
volume = "95",
pages = "1201--9",
journal = "International Journal of Radiation Oncology Biology Physics",
issn = "0360-3016",
publisher = "Elsevier Inc.",
number = "4",

}

TY - JOUR

T1 - Impact of Sequencing Radiation Therapy and Chemotherapy on Long-Term Local Toxicity for Early Breast Cancer

T2 - Results of a Randomized Study at 15-Year Follow-Up

AU - Pinnarò, Paola

AU - Giordano, Carolina

AU - Farneti, Alessia

AU - Strigari, Lidia

AU - Landoni, Valeria

AU - Marucci, Laura

AU - Petrongari, Maria Grazia

AU - Sanguineti, Giuseppe

N1 - Copyright © 2016 Elsevier Inc. All rights reserved.

PY - 2016/7/15

Y1 - 2016/7/15

N2 - 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.

AB - 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.

KW - Journal Article

U2 - 10.1016/j.ijrobp.2016.03.016

DO - 10.1016/j.ijrobp.2016.03.016

M3 - Article

VL - 95

SP - 1201

EP - 1209

JO - International Journal of Radiation Oncology Biology Physics

JF - International Journal of Radiation Oncology Biology Physics

SN - 0360-3016

IS - 4

ER -