Most patients typically develop only minimal skin fibrosis after their radiation therapy, however for those who have a more significant degree of fibrosis I often recommend a combination of vitamin E (400 I.U, twice a day) and pentoxifylline (400 mg, three times each day).
Fibrosis can develop months-to-years after radiation therapy to any region of the body, but is most common in the extremities, breasts (read more about implant contracture, below) and head and neck where higher radiation doses are often required on or just below the skin surface.
How does this treatment work?
It is not entirely clear how these molecules work to reduce fibrosis.
Vitamin E may act as a antioxidant, helping to prevent ongoing free radical damage to the radiated tissues.
Pentoxifylline may be involved in blocking the molecular signaling pathway that is responsible for the development of fibrosis as a response to inflammation and injury. Additionally, pentoxifylline increases the flexibility and permeability of red blood cells which enables them to more easily bring oxygen to the tissues and carry carbon dioxide away. It is because of this mechanism that pentoxifylline is used in the management of peripheral artery disease, leg ulcers, strokes, high-altitude sickness, eye and ear disorders, and sickle cell disease and diabetic neuropathy.
Results of treatment:
Significant improvement in pain, tightness, muscle strength, edema and range of motion have all been reported with this treatment.
It seems that the earlier that this treatment is started after the development of fibrosis the quicker the response, however this combination therapy is still effective (approximately 60-70% reduction in fibrosis) even when started many years after radiation therapy.
It is important to recognize that this medication combination can take 6-48 months to achieve the best possible results. In one study, it took a median of 16 months to achieve a 68% reduction in fibrosis for those who started treatment within 6 years of completing radiation therapy and a median of 28 months for those who started treatment greater than 6 years after completing radiation therapy. Relapses were found to occur more commonly among patients who took this treatment for less than 12 months.
Duration of treatment:
- For severe skin fibrosis, I recommend that treatment continue for 3 or more years.
- For mild-to-moderate fibrosis, I recommend that treatment continue for at least 1 year.
An increasingly common issue: Breast implant contracture following radiation therapy
As more patients undergo breast reconstruction (with either tissue transfer/rotational techniques or implant prostheses), it has become more common in oncology and plastic surgery practices to have to address breast cancer treatments in this setting.
All patients with breast implants or expanders will eventually develop scar tissue (fibrosis) surrounding the prosthesis as a consequence of the body’s normal immune/inflammatory response to a foreign body. This fibrotic response varies in severity among individuals, but it is estimated that up to 25% of women with breast implants undergo revision surgery (at 10 years) due to implant contracture (shrinking and or hardening of tissue surrounding the implant). Following radiation therapy, implant contracture rates are increased due to the effects of radiation fibrosis. (picture on left: This patient developed an implant contracture after radiation therapy to to her right breast and implant. The superior implant displacement and circumferential tightening are common findings.)
Although the rates or lower in women who select breast reconstruction with their own tissues (tissue transfer or rotational techniques), they are also at a higher risk of developing contracture and fibrosis of their reconstructed breast after radiation therapy to these tissues.
Vitamin E and pentoxifylline are being investigated as a prophylactic therapy to reduce the incidence and severity of implant contractures or implant loss after receiving radiation therapy to the chest wall or breast in the setting of breast cancer treatment. The results of these investigations will be important in helping us better direct our management of this condition.
Starting this treatment during radiation therapy is not recommended, as vitamin E may reduce the efficacy of radiation.
Vitamin E and pentoxifylline is a useful therapy for patients with radiation-induced fibrosis. It can reduce the signs and symptoms of this condition dramatically in the majority of those who continue taking it for at least 6-12 months (or longer in cases of severe, long-standing fibrosis.)
The use of vitamin E and pentoxifylline following radiation therapy to reduce the risk of breast implant contracture and failure is under investigation.
If you think that you might benefit from a course of vitamin E and pentoxifylline, discuss this with you radiation oncologist.