International Journal of Radiation Oncology*Biology*Physics
Clinical InvestigationRandomized Trial of Pentoxifylline and Vitamin E vs Standard Follow-up After Breast Irradiation to Prevent Breast Fibrosis, Evaluated by Tissue Compliance Meter
Introduction
Excluding skin cancer, breast cancer is the most common cancer in American women. It is estimated that in 2011 more than 230,000 invasive breast cancers and more than 57,000 noninvasive breast cancers will be diagnosed in the United States (1). Women with early breast cancer may be treated with breast conservation, which usually includes limited surgery followed by breast irradiation. Women treated with mastectomy may have indications for postoperative radiation based on tumor size, lymph node involvement, or other adverse factors. The death rate in the United States from breast cancer has been decreasing since 1990, and there are more than 2.6 million breast cancer survivors. Because many patients will live for decades after completing treatment, minimizing side effects of treatment and maintaining quality of life are extremely important.
Radiation-induced fibrosis (RIF) is a common side effect of therapeutic irradiation that can result in pain, poor cosmesis, and functional impairment. Previously, RIF was considered irreversible. Pentoxifylline (PTX) combined with vitamin E has been demonstrated in both preclinical and clinical studies to reverse chronic RIF. Delanian et al (2) performed a placebo-controlled trial of combined PTX and tocopherol in women who had clinically measurable RIF after radiation therapy for breast cancer and demonstrated reversal of RIF in the treated group. This work supported the concept of RIF as a modifiable, and possibly preventable, process. We conducted an institutional randomized clinical trial to determine whether PTX and vitamin E, both given orally for 6 months after completion of breast or chest wall irradiation, was effective in preventing regional RIF. Clinical assessment of fibrosis is qualitative and subjective. We selected the tissue compliance meter (TCM) as a quantitative assessment of tissue compliance to measure fibrosis. The TCM is a hand-held device that was developed for physical therapy assessment and validated for quantitative assessment of tissue compliance in breast tissue (3). We measured postradiation therapy tissue compliance in the treated and untreated breast/chest wall with a TCM (4).
Section snippets
Methods and Materials
This prospective, randomized study was approved by our institutional review board IRB-01 (biomedical). Eligible subjects were patients with breast cancer treated with breast conservation or after mastectomy, without metastatic disease. Informed consent was obtained before study entry. The trial utilized a block randomization with a block size of 4 and 6 and an allocation ratio of 1:1 (control: study intervention). The study used convenience sampling; all eligible patients were approached
Results
The majority of patients (47 of 53) were treated with breast conservation: lumpectomy and sentinel node sampling or axillary lymph node dissection, followed by radiation to the whole breast.
Six patients were treated after mastectomy (Table 1). No attempt was made to stratify patients according to hormone or chemotherapy treatment. However, the differences between these treatment factors in the 2 groups were not significant: 9 of 26 study patients and 13 of 27 control patients had chemotherapy
Discussion
Radiation-induced fibrosis is a chronic late effect of therapeutic radiation that, until the 1990s, was considered irreversible. Preclinical work at this institution demonstrated that PTX reduced the incidence and severity of late radiation injury in the mouse extremity (8). Lefaix et al (9) demonstrated that PTX and vitamin E enhanced healing of full-thickness skin grafts in irradiated pigskin. A clinical pilot study at this institution indicated that PTX was effective in healing soft-tissue
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2022, Advances in Radiation OncologyCitation Excerpt :We excluded 2094 after title and abstract analysis and 7 after reading the full text. Nine publications (7 studies) were included: Bourgeois et al,7 Brooker et al19 and their protocol NCT00041223,30 Delanian et al,12 Gothard et al,14 Jacobson et al16 and their protocol NCT00583700,31 Magnusson et al15 and Oliveira et al.8 The main characteristics of the 7 included studies are presented in Table 1. After judging the risk of bias, we observed methodological limitations with high risk of bias in 18% of the domains.
Conflict of interest: none.