Treatment of radiation-induced fibrosis of the face with manual compression therapy.

Abstract

Radiation-induced fibrosis (RIF) is an uncommon complication of radiation therapy. RIF most often occurs in the extremities; it is rare in the head and neck. Only a few medical treatments for RIF are available, and they have been mediocre at best. We describe a case of RIF of the face that was treated successfully with a nonmedical modality: manual compression therapy.

Introduction

Radiation-induced fibrosis (RIF) is an uncommon complication of radiation therapy. Although radiation damage to the soft tissue has been reported to occur in as many as 40% of patients, RIF accounts for only a small fraction of these cases. (1) RIF can occur as a late sequela of radiotherapy, sometimes appearing as late as 20 years after the inciting event. RIF is a consequence of radiotherapy for many types of cancer, and it can involve various regions of the body, but it rarely occurs in the head and neck. Most studies of RIF have been conducted in women with breast cancer.

Several therapies for RIF have been attempted during the past 10 years with varying degrees of success. The most common therapy in use today is a combination of pentoxifylline and tocopherol (vitamin E), which has been used since the early 1990s. This combination has been associated with a regression rate of 64%. (2) More recently, low-dose interferon gamma has been used in small studies with good results after 6 and 12 months. (3) Even so, there is no optimal treatment for this disease.

In this article, we describe a case of RIF of the face that was treated successfully with manual compression therapy.

Case report

We evaluated a 59-year-old man who in August 1987 had undergone a total laryngectomy and right modified radical neck dissection for a T2N1M0 squamous cell carcinoma of the right false vocal fold. In July 1988, he underwent a left radical neck dissection. In August 1999, he was found to have a large T3N2B squamous cell carcinoma in the left tonsil. He then underwent a full course of radiotherapy to 7,440 cGy, which he completed in October 1999. He experienced a complete response to treatment.

In December 2000, however, the patient began to exhibit facial edema, which progressed fairly rapidly to encompass his entire face (figure, A). Magnetic resonance imaging revealed no pathology that might account for this condition, and the man was diagnosed with RIF of the face. Treatment with pentoxifylline and tocopherol was initiated, but after 6 months, no improvement was noted. He was then referred for manual compression therapy for lymphedema (see "Manual compression technique" in the "Discussion" section for a description of the technique that was used).

[FIGURE A OMITTED]

Compression therapy resulted in a dramatic improvement within 2 weeks (figure, B). However, the costs and logistics involved in treatment proved to be more daunting than the patient would tolerate, and he eventually discontinued treatment. The edema returned following the cessation of therapy.

[FIGURE B OMITTED]

Discussion

Factors related to the onset of RIF include the size of the total radiation dose and the irradiated volume, the patient's medical history, and the use of concomitant chemotherapy. (2) Once RIF occurs, there is no spontaneous regression. RIF is believed to be caused by an increase in the production of collagen in both the cutaneous and subcutaneous tissues and subsequent chronic cellular activation and remodeling. (3,4) This process leads to retraction of affected tissues and a conversion of the tissue that is consistent with sclerosis. Tissue affected by RIF is characterized by a disorganized extracellular matrix, an excess of myofibroblasts, and a marked upregulation of collagen synthesis. (4,5) The excess production of collagen has been linked to elevated levels of transforming growth factor beta (TGF-[beta]). Excess amounts of TGF-[beta] induce an increase in myofibroblast production of collagens I, III, and IV. (5) This increase leads to the formation of thick fibrotic tissue and causes contractures of and damage to the lymphatic vessels? (3,4)

Treatment. The rationale for using pentoxifylline and tocopherol to treat RIF is based on the idea that ionizing radiation leads to the production of free radicals in living tissue. Several studies have shown that these two agents together lead to a regression of radiotherapy damage. (2,3) Delanian et al used doses of 800 mg/day of pentoxifylline and 1,000 IU/day of tocopherol for at least 6 months in 43 patients and found a 64% regression of RIF at study's end. (2) These doses were chosen to avoid severe adverse reactions in vascular patients, to provide sufficient antioxidant activity for the irradiation of free radicals, and to reduce the TGF-[[beta].sub.1] level.

More recently, Gottlober et al used low-dose interferon gamma at 100 [micro]g three times per week subcutaneously for 6 months and then once weekly for 6 months as a treatment for RIF. (3) They found that this regimen led to a reduction in skin thickness with possible reorganization of the local lymphatics and better lymph drainage. Interferon gamma inhibits the activity of fibroblasts in the cutaneous and subcutaneous regions and thereby decreases the synthesis of collagen I, collagen II, and TGF-[[beta].sub.1]. (3)

Manual compression therapy has been found to be quite effective for RIF, mainly in the extremities. (5) This therapy involves the use of noninvasive directed massage to drain the lymphatic fluid from the affected extremity through the superficial lymph vessels. Our patient was referred for manual compression therapy of the head and neck because other treatments had failed.

Lymphatic anatomy. Knowledge of the anatomy of the facial lymphatic system is important to understanding compression therapy. The face is divided into two parts: the upper and outer lymphotome and the middle lymphotome. (In the body, lymphotomes are referred to in terms of trunk quadrants.) Within the facial lymphotomes, fluid (lymph) flows through the lymphatic vessels in specific directions. Fluid in the upper and outer lymphotome drains outward and downward into the parotid nodes, then down the cervical chain to the venous angle or terminus that is accessed at the supraclavicular fossae, and finally into the bloodstream. The middle lymphotome drains lymph into the submandibular nodes, then down the cervical chain to the terminus, and finally into the bloodstream.

The dividing line between the two facial lymphotomes is a network of vessels known as the watershed or anastomosis. These vessels are patent but not functional. Because of the pressure gradients and flow forces within the lymphotomes, fluid does not cross the watershed in a healthy, normal person. But altering the flow with specific massage techniques opens the anastomoses and allows the lymph to traverse from one lymphotome to the other, thereby promoting lymph drainage.

Manual compression technique. Altering lymphatic drainage in this manner can be accomplished by performing a light superficial hand massage and then applying a compression bandage. In our patient, we applied short, low-stretch bandages to the face to reduce the amount of protein-rich fluid in the swollen tissues. These kinds of bandages exert a high degree of working pressure and a low amount of resting pressure.

Because our patient's lymphatic system was overburdened, he experienced skin changes. Therefore, skin care was provided during each of 41 treatment sessions. Also, the patient and his family were taught how to perform a skin check and instructed to do so daily. They were taught to look for cuts, abrasions, and skin breakdown and to pay particular attention to all skin folds. Moreover, because the patient's immune response was diminished, he and his family were taught how to recognize the signs of infection. Finally, they were made aware of the urgency of seeking medical attention should any sign of infection arise.

The patient was also given therapeutic exercises, including facial flexibility and range-of-motion maneuvers, to enhance lymph drainage. These exercises also facilitate drainage while the patient is wearing compression bandages.

We provided assistance in selecting medical compression garments and supplies so that the patient could maintain a therapy program at home. He was fitted with a custom head and neck garment. Initially, the garment had cut-outs for both the eyes and mouth, but the patient preferred to wear a garment without a mouth opening. As a result, and because fluid travels the path of least resistance, lymph began to settle in his eyelid. In response, we placed a high-density foam pad over his left eye to provide compression. The patient found the garment very uncomfortable and confining, but he noticed a significant reduction of the edema within 2 weeks.

References

(1.) Fischer M, Wohlrab J, Marsch W. Crux medicorum ulcerated radiation-induced fibrosis--successful therapy with pentoxifylline and vitamin E. Eur J Dermatol 2001; 11:38-40.

(2.) Delanian S, Balla-Mekias S, Lefaix JL. Striking regression of chronic radiotherapy damage in a clinical trial of combined pentoxifylline and tocopherol. J Clin Oncol 1999; 17:3283-90.

(3.) Gottlober P, Steinert M, Bahren W, et al. Interferon-gamma in 5 patients with cutaneous radiation syndrome after radiation therapy. Int J Radiat Oncol Biol Phys 2001;50:159-66.

(4.) Martin M, Delanian S, Sivan V, et al. [Radiation-induced superficial fibrosis and TGF-beta 1]. Cancer Radiother 2000;4:369-84.

(5.) Riekki R, Jukkola A, Sassi ML, et al. Modulation of skin collagen metabolism by irradiation: Collagen synthesis is increased in irradiated human skin. Br J Dermatol 2000;142:874-80.

From the Department of Surgery, Carl T. Hayden VA Medical Center, Phoenix, and the Lymphedema Treatment Center, Phoenix Baptist Hospital and Medical Center.

Reprint requests: Randy Oppenheimer, MD, Section of Otolaryngology-Head and Neck Surgery, Department of Surgery, Carl T. Hayden VA Medical Center, 650 E. Indian School Rd., Phoenix, AZ 85012. Phone: [phone]; fax: [phone]; e-mail: [e-mail]