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      Radiation-Associated Angiosarcoma After Breast Cancer: High Recurrence Rate and Poor Survival Despite Surgical Treatment with R0 Resection

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          Abstract

          Background

          Secondary angiosarcoma of the breast is a rare but severe long-term complication of breast cancer treated with breast-conserving surgery and radiotherapy. We characterized a population-based cohort of patients with secondary angiosarcomas from two tertiary hospitals to investigate this complication with respect to surgical treatment and outcome.

          Methods

          We identified 35 patients with a history of radiation for breast cancer that developed angiosarcoma in the irradiated field from 1990 to 2009. Of these, 31 underwent surgery and were included for analysis.

          Results

          Angiosarcoma developed after median 7 years (range 3–25 years). R0 resection was obtained in 23 of 31 patients after primary treatment. Local recurrence developed in 19 patients after median 6 months (range 1–89 months). Regional and distant metastases occurred in 13 patients after median 17 months (range 2–50 months); nine which also had local recurrence. Patients whose local recurrence could be operated on had a better survival after treatment than those who were not considered for surgical treatment, median 34 months (range 6–84 months) compared with 6 months (range 5–24 months). The median disease-free survival and disease-specific survival was 16 and 37 months, respectively.

          Conclusions

          Despite R0 resection, two-thirds of the patients developed a local recurrence. Survival among those with local recurrence was better if the patient could be treated with surgery. Overall, the prognosis was dismal and median DSS was just over 3 years.

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          Most cited references26

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          Impact of a higher radiation dose on local control and survival in breast-conserving therapy of early breast cancer: 10-year results of the randomized boost versus no boost EORTC 22881-10882 trial.

          To investigate the long-term impact of a boost radiation dose of 16 Gy on local control, fibrosis, and overall survival for patients with stage I and II breast cancer who underwent breast-conserving therapy. A total of 5,318 patients with microscopically complete excision followed by whole-breast irradiation of 50 Gy were randomly assigned to receive either a boost dose of 16 Gy (2,661 patients) or no boost dose (2,657 patients), with a median follow-up of 10.8 years. The median age was 55 years. Local recurrence was reported as the first treatment failure in 278 patients with no boost versus 165 patients with boost; at 10 years, the cumulative incidence of local recurrence was 10.2% versus 6.2% for the no boost and the boost group, respectively (P < .0001). The hazard ratio of local recurrence was 0.59 (0.46 to 0.76) in favor of the boost, with no statistically significant interaction per age group. The absolute risk reduction at 10 years per age group was the largest in patients
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            Phase II trial of weekly paclitaxel for unresectable angiosarcoma: the ANGIOTAX Study.

            The objective of this phase II trial was to assess the efficacy and toxicity of weekly paclitaxel for patients with metastatic or unresectable angiosarcoma. Thirty patients were entered onto the study from April 2005 through October 2006. Paclitaxel was administered intravenously as a 60-minute infusion at a dose of 80 mg/m(2) on days 1, 8, and 15 of a 4-week cycle. The primary end point was the nonprogression rate after two cycles. The progression-free survival rates after 2 and 4 months were 74% and 45%, respectively. With a median follow-up of 8 months, the median time to progression was 4 months and the median overall survival was 8 months. The progression-free survival rate was similar in patients pretreated with chemotherapy and in chemotherapy-naïve patients (77% v 71%). Three patients with locally advanced breast angiosarcoma presented partial response, which enabled a secondary curative-intent surgery with complete histologic response in two cases. One toxic death occurred as a result of a thrombocytopenia episode. Six patients presented with grade 3 toxicities and one patient presented with a grade 4 toxicity. Anemia and fatigue were the most frequently reported toxicities. Weekly paclitaxel at the dose schedule used in the current study was well tolerated and demonstrated clinical benefit.
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              The UK Standardisation of Breast Radiotherapy (START) Trial A of radiotherapy hypofractionation for treatment of early breast cancer: a randomised trial

              (2008)
              Summary Background The international standard radiotherapy schedule for breast cancer treatment delivers a high total dose in 25 small daily doses (fractions). However, a lower total dose delivered in fewer, larger fractions (hypofractionation) is hypothesised to be at least as safe and effective as the standard treatment. We tested two dose levels of a 13-fraction schedule against the standard regimen with the aim of measuring the sensitivity of normal and malignant tissues to fraction size. Methods Between 1998 and 2002, 2236 women with early breast cancer (pT1-3a pN0-1 M0) at 17 centres in the UK were randomly assigned after primary surgery to receive 50 Gy in 25 fractions of 2·0 Gy versus 41·6 Gy or 39 Gy in 13 fractions of 3·2 Gy or 3·0 Gy over 5 weeks. Women were eligible if they were aged over 18 years, did not have an immediate surgical reconstruction, and were available for follow-up. Randomisation method was computer generated and was not blinded. The protocol-specified principal endpoints were local-regional tumour relapse, defined as reappearance of cancer at irradiated sites, late normal tissue effects, and quality of life. Analysis was by intention to treat. This study is registered as an International Standard Randomised Controlled Trial, number ISRCTN59368779. Findings 749 women were assigned to the 50 Gy group, 750 to the 41·6 Gy group, and 737 to the 39 Gy group. After a median follow up of 5·1 years (IQR 4·4–6·0) the rate of local-regional tumour relapse at 5 years was 3·6% (95% CI 2·2–5·1) after 50 Gy, 3·5% (95% CI 2·1–4·3) after 41·6 Gy, and 5·2% (95% CI 3·5–6·9) after 39 Gy. The estimated absolute differences in 5-year local-regional relapse rates compared with 50 Gy were 0·2% (95% CI −1·3% to 2·6%) after 41·6 Gy and 0·9% (95% CI −0·8% to 3·7%) after 39 Gy. Photographic and patient self-assessments suggested lower rates of late adverse effects after 39 Gy than with 50 Gy, with an HR for late change in breast appearance (photographic) of 0·69 (95% CI 0·52–0·91, p=0·01). From a planned meta-analysis with the pilot trial, the adjusted estimates of α/β value for tumour control was 4·6 Gy (95% CI 1·1–8·1) and for late change in breast appearance (photographic) was 3·4 Gy (95% CI 2·3–4·5). Interpretation The data are consistent with the hypothesis that breast cancer and the dose-limiting normal tissues respond similarly to change in radiotherapy fraction size. 41·6 Gy in 13 fractions was similar to the control regimen of 50 Gy in 25 fractions in terms of local-regional tumour control and late normal tissue effects, a result consistent with the result of START Trial B. A lower total dose in a smaller number of fractions could offer similar rates of tumour control and normal tissue damage as the international standard fractionation schedule of 50 Gy in 25 fractions.
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                Author and article information

                Contributors
                h.j.hoekstra@umcg.nl
                Journal
                Ann Surg Oncol
                Ann. Surg. Oncol
                Annals of Surgical Oncology
                Springer-Verlag (New York )
                1068-9265
                1534-4681
                31 March 2012
                31 March 2012
                August 2012
                : 19
                : 8
                : 2700-2706
                Affiliations
                [1 ]Department of Surgical Oncology, University of Groningen University Medical Center, Groningen, The Netherlands
                [2 ]Department of Pathology, University of Groningen University Medical Center, Groningen, The Netherlands
                [3 ]Department of Orthopedics, Lund University, Lund University Hospital, Lund, Sweden
                Article
                2310
                10.1245/s10434-012-2310-x
                3404270
                22466664
                1880f240-bf4c-4275-b1e5-94263c1721dc
                © The Author(s) 2012
                History
                : 17 August 2011
                Categories
                Bone and Soft Tissue Sarcomas
                Custom metadata
                © Society of Surgical Oncology 2012

                Oncology & Radiotherapy
                Oncology & Radiotherapy

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