After radiotherapy for breast cancer, approximately one in 1000 women will go on to develop radiotherapy-associated angiosarcoma (RAAS), and surgery alone is sufficient to treat the disease in most cases.
These findings come from the largest single cohort to date to study this development, published as a research letter in JAMA Oncology on January 24.
"As clinicians, we should be aware of the fact that there is a risk for an angiosarcoma, that it does not occur in patients who do not receive radiation, and that we should inform patients before radiotherapy about this rare, but serious, late complication," commented lead author Anouk J. M. Rombouts, MD, department of surgery, Radboud University Medical Center, Nijmegen, the Netherlands.
Angiosarcoma is a form of soft-tissue sarcoma, in which the cells that make up the lining of the blood vessels grow and multiply abnormally to form a tumor.
Rombouts and colleagues looked for RAAS in a cohort of almost 300,000 breast cancer patients. They found that 0.1% of women treated with radiotherapy developed the complication, with older women more at risk. The majority of the women who developed angiosarcoma underwent surgery alone, although some had various treatment combinations. The overall 5-year survival rate was approximately 40%, confirming findings from previous, smaller studies, the authors comment.
Rombouts told Medscape Medical News that an important aspect of the study is that the risk of developing RAAS "is there but it's a low chance."
She said, "The benefits of radiotherapy exceed the risk of developing an angiosarcoma, and therefore we should not change follow-up schemes or stop treating patients with radiotherapy."
"However, we now have more information, which we can use to inform the patient before treatment," she added.
As to how patients who develop RAAS should be treated, Rombouts said that, while surgery is the most common choice, there is not enough literature available to say definitively whether or not radiotherapy should also be given. Consequently, she believes that patients should be treated on an individual basis. "Because of the low incidence of RAAS, and as a result, the lack of literature available, it's hard to tell which treatment should be given," she said.
"Our study showed that patients treated with surgery had better prognosis than patients who did not undergo surgery. We would therefore advise surgical treatment in all RAAS patients who are fit for surgery. Unfortunately, only a small number of patients underwent (neo)adjuvant therapy, and a relation between survival and chemotherapy or radiotherapy could not be confirmed," she added.
Rare but Serious Complication
Previous studies have indicated that RAAS is a rare, but serious, complication of radiotherapy for breast cancer.
However, Rombouts pointed out that "the numbers described in the literature are indeed really low."
While one review by Depla and colleagues included 222 patients, these came from a total of 74 articles, with each individual study consisting of a small number of participants.
For the current study, the team assembled the largest cohort to date, drawing on the nationwide Netherlands Cancer Registry to examine all patients with stages I–III primary breast cancer who were treated with or without radiotherapy between 1989 and 2015. The total population consisted of 295,577 patients who had a median age at diagnosis of 58 years and a median follow-up after breast cancer diagnosis of 7.7 years. The researchers report that, of the 111,754 patients who did not receive radiotherapy, none developed angiosarcoma.
In contrast, 209 (0.1%) of the 184,823 patients who received radiotherapy developed RAAS of the breast and/or chest wall, at a mean latency of 8 years and a median of 6 years.
Patients who were older when they received the diagnosis of breast cancer were at an increased risk of developing RAAS, at a hazard ratio of 1.05 versus younger patients.
In addition, patients who underwent mastectomy for the primary tumor were less likely to develop RAAS than those who had breast-conserving therapy, at a hazard ratio of 0.22.
Of the 194 patients for whom RAAS treatment data was available, 166 (79.4%) underwent surgery only and 19 (9.1%) had surgery and radiotherapy, which was combined with hyperthermia therapy in 13 patients.
A further three (1.4%) patients had surgery plus chemotherapy and six (2.9%) had chemotherapy or radiotherapy alone.
Irrespective of treatment, RAAS was associated with an overall 5-year survival rate of 40.5%, falling to 25.2% at 10 years.
Adding radiotherapy to surgery for the treatment of RAAS did not significantly improve survival, at a hazard ratio of 0.61.
The team writes: "A beneficial effect on overall survival of the addition of [radiotherapy] to the treatment of RAAS could not be confirmed in this population-based analysis, and evidence in the literature also lacks power to draw firm conclusions."
"This study demonstrates that the low incidence of RAAS renders a prospective analysis practically not feasible."
Instead, the researchers are interested in establishing a prospective database or registry to provide more information on the incidence, treatment, and outcomes of RAAS. To those ends, Rombouts said that she and her colleagues have some "unanswered questions" from the current findings that they would like to investigate further before reaching out to the international community. "We will have to investigate whether there's interest in the international community for opening such a registry," she said.
"However, given the low incidence of RAAS, we believe that a prospective registry would be the only way to find out more about this rare but serious complication of radiotherapy in breast cancer patients."
The authors have disclosed no relevant financial relationships.
JAMA Oncology. Published online January 24, 2019. Abstract
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