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(Radiology. 2001;218:834-839.)
© RSNA, 2001

Radiation Oncology

Radiation Therapy for Life- or Function-threatening Infant Hemangioma1

Ichiro Ogino, MD, Katsuyuki Torikai, MD, Shinji Kobayasi, MD, Noriko Aida, MD, Masaharu Hata, MD and Hisato Kigasawa, MD

1 From the Departments of Radiology (I.O., N.A., M.H.), Plastic and Reconstructive Surgery (K.T., S.K.), and Hematology (H.K.), Kanagawa Children’s Medical Center, Yokohama, Japan. Received January 17, 2000; revision requested March 5; final revision received July 10; accepted August 2. I.O. supported by a grant from the Children’s Cancer Association of Japan. Address correspondence to I.O., Department of Radiology, Yokohama City University, School of Medicine, 3-9 Fukuura, Kanazawa-ku, Yokohama, 236-0004 Japan (e-mail: oginoro@med.yokohama-cu.ac.jp).


   ABSTRACT
TOP
 ABSTRACT
INTRODUCTION
 MATERIALS AND METHODS
 RESULTS
 DISCUSSION
 REFERENCES
 
PURPOSE: To assess the effectiveness and long-term results of radiation therapy in infants with life- or function-threatening hemangiomas.

MATERIALS AND METHODS: Thirteen patients with life- or function-threatening hemangiomas (eight male, five female; age range, 0–8 months; median age, 2 months) were treated with radiation therapy. Life-threatening hemangiomas were treated with five fractions of radiation per week, and function-threatening hemangiomas were treated with two fractions per week. A median dose of 10 Gy was delivered to each hemangioma. The presence of residual hemangiomas, skin changes, functional problems, and growth delay was evaluated.

RESULTS: All patients with Kasabach-Merritt syndrome (KMS) showed regression of the hemangioma and an increase in platelet counts to greater than 100,000 per cubic millimeter (1.0 x 1011 per liter) within 40 days after radiation therapy. The treatment field was inadequate in two patients who required reirradiation or a change of treatment portal. With the exception of the patients with KMS, all but one patient experienced relief from symptoms in 40 days. Severe long-term radiation-related morbidity was noted in one patient who required reirradiation for a relapsed hemangioma.

CONCLUSION: Radiation therapy (in doses of <=10 Gy in 2-Gy fractions) is indicated for life-threatening hemangiomas and for some function-threatening hemangiomas.

Index terms: Angioma, soft tissues, 9*.312 • Therapeutic radiology, in infants and children


   INTRODUCTION
TOP
 ABSTRACT
 INTRODUCTION
MATERIALS AND METHODS
 RESULTS
 DISCUSSION
 REFERENCES
 
Hemangiomas of the skin and subcutaneous tissue represent the most common benign tumors in infants. The annual incidence seems to be greater than 0.45% (1). Hemangiomas exhibit a characteristic pattern of rapid proliferation and slow spontaneous involution. Complete resolution of hemangiomas has been reported (2,3) to occur in approximately 49% of children by age 5 years and in 72% by age 7 years, and continued improvement is expected to age 12 years. Only minor skin changes remain after regression in the majority of the patients.

The majority of hemangiomas are small and asymptomatic, and observation is indicated. However, 10%–20% of cases are function-threatening due to local compression and displacement of adjacent organs (4). Hemangiomas may threaten the patient’s life because they are associated with congestive heart failure, acute respiratory distress, or platelet consumption (Kasabach-Merritt syndrome [KMS]) (5–7). These hemangiomas require prompt attention and treatment.

The management of life- or function-threatening hemangiomas is often difficult. Treatment methods that have been used include surgical resection, corticosteroid therapy, embolization, laser surgery, and radiation therapy. However, to our knowledge, there is little available information regarding the long-term results of these methods. Historically, radiation therapy has been the preferred method for the treatment of hemangiomas because they are radiosensitive, and they are more so if they are treated earlier in life (8–10).

In recent years, the use of radiation therapy has decreased with the recognition of late risks associated with irradiation of these benign lesions, and many of these lesions regress spontaneously (11–13). However, in certain situations, radiation therapy is indicated. The purpose of our study was to assess the effectiveness and long-term results of treatment in a group of patients with life- and function-threatening hemangiomas treated with irradiation. To our knowledge, this work represents the largest number of patients treated with radiation therapy for life- or function-threatening infant hemangioma, including KMS.


   MATERIALS AND METHODS
TOP
 ABSTRACT
 INTRODUCTION
 MATERIALS AND METHODS
RESULTS
 DISCUSSION
 REFERENCES
 
Fourteen patients with life- and function-threatening infant hemangiomas received radiation therapy at our institution between May 1974 and August 1985. One patient with KMS who had received external irradiation at another institution and who received reirradiation for a recurrent lesion at our institution was excluded from this study. A retrospective analysis was conducted in the remaining 13 patients (eight male, five female; age range, 0–8 months; median age, 2 months), who at the time of radiation therapy were younger than 9 months of age and who had life- or function-threatening hemangiomas. Appropriate informed consent was obtained from the parents. The study was conducted according to the principles of the Declaration of Helsinki.

Table 1 summarizes the characteristics of the patients. The tumor sites were the extremities in four patients, the trunk in three, and the face in six. Tumors ranged from 1.5 to 9.5 cm in greatest diameter (median diameter, 6 cm). Rapidly growing hemangiomas caused symptoms in all 13 patients. Symptoms included consumption coagulopathy (ie, KMS) in eight patients, aspiration pneumonia in one, inability to use a hand in one, obstruction of vision in one, vomiting and difficulty in eating in one, and hemorrhage and obstruction of vision in one.


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  		TABLE 1. Patient Characteristics
 
Three patients had pathologically confirmed hemangiomas, and the other 10 had clinically diagnosed hemangiomas. In three patients, corticosteroid treatment failed to improve the hemangiomas before radiation therapy. Corticosteroid treatment did not improve either the size of the hemangioma or the symptoms in patients 2 and 9. Hemangioma progressed when steroid therapy was discontinued in patient 13, who required a blood transfusion for hemorrhage.

External irradiation was delivered by using a 6-MeV electron beam or a 6-MV photon beam. Two patients (patients 4 and 9) were treated with 6-MeV electron-beam irradiation, and 11 were treated with 6-MV photon-beam irradiation. Treatment portals were aimed for a dose delivery to the hemangiomas with better sparing of normal tissue by electrons and tangential-field photons.

Life-threatening hemangiomas were treated with five fractions per week, and function-threatening hemangiomas were treated with two fractions per week. In patient 3, the platelet count was 64,000 per cubic millimeter (6.4 x 1010 per liter), and radiation therapy was delivered in two fractions per week. Radiation therapy was delivered in five fractions per week in the other seven patients with KMS whose platelet counts were less than 50,000 per cubic millimeter (5.0 x 1010 per liter). Most patients received a daily dose of 2 Gy. Doses ranging from 6 to 18 Gy (median dose, 10 Gy) were delivered to the hemangiomas. Most patients with slow improvement of symptoms during radiation therapy received more than 10 Gy, and most patients with rapid improvement of symptoms received less than 10 Gy.

Follow-up ranged from 14 to 24 years (median follow-up, 19 years). Follow-up included review of the institutional records, telephone contact, and occasional direct communication with the patient or parents. To determine the effectiveness of treatment and long-term results, we evaluated the presence of residual hemangiomas, skin changes, functional problems, and growth delay.


   RESULTS
TOP
 ABSTRACT
 INTRODUCTION
 MATERIALS AND METHODS
 RESULTS
DISCUSSION
 REFERENCES
 
Table 2 shows the results of radiation therapy in patients with KMS. In all patients, hemangioma regressed and platelet counts increased to 100,000 per cubic millimeter (1.0 x 1011 per liter) within 40 days after initiation of radiation therapy. The treatment field was inadequate in two patients (patients 2 and 4) who required reirradiation or a change of treatment portal.


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  		TABLE 2. Results in Patients with KMS
 
In patient 2, the hemangioma, which was located in the right anterior shin, was successfully treated with opposed lateral portals to avoid irradiating the long bones with 6-MV photons. However, the hemangioma relapsed from the posterior margin of the radiation field, and the platelet count decreased to 36,000 per cubic millimeter (3.6 x 1010 per liter) within 53 days after initiation of radiation therapy. This patient received an additional dose of 12 Gy in four fractions, and the platelet count increased to 150,000 per cubic millimeter (1.5 x 1011 per liter) within 38 days after reirradiation.

In patient 4, the hemangioma extended indistinctly to ecchymoses in the back. This patient received 10 Gy to the tumor, but the platelet count did not increase, and the tumor grew in the ecchymotic area where radiation was not delivered. An additional 6 Gy was delivered to the ecchymotic area. The platelet count increased to 100,000 per cubic millimeter (1.0 x 1011 per liter) within 14 days after extended-field irradiation.

Table 3 shows the results of radiation therapy in the symptomatic patients, with the exception of patients with KMS. All symptoms were relieved. Relief of symptoms occurred in all but one patient in 40 days. In patient 11, a life-threatening hemangioma was treated with five fractions per week, and symptoms improved in 5 days. Tumors completely regressed without further treatment in all but one patient. A residual tumor in the face was excised for cosmesis in patient 13 (Fig 1). (This patient may require surgical scar revision but was satisfied with the cosmetic results when this article was written.) In two patients who received radiation therapy for obstruction of vision, vision was normal at last follow-up.


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  		TABLE 3. Results in Symptomatic Patients without KMS
 


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  		Figure 1a. (a) Four-month-old patient with hemangioma prior to radiation therapy. Corticosteroid therapy was indicated, and the hemangioma regressed. However, the hemangioma rapidly progressed after corticosteroid therapy was withdrawn. (b) Two months after radiation therapy, the tumor has decreased in size, and vision was no longer obstructed. (c) Patient at age 5 years, prior to surgery. (d) Patient at age 10 years, 5 years after surgery. (Permission to publish photographs was granted by the parents.)

 


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  		Figure 1b. (a) Four-month-old patient with hemangioma prior to radiation therapy. Corticosteroid therapy was indicated, and the hemangioma regressed. However, the hemangioma rapidly progressed after corticosteroid therapy was withdrawn. (b) Two months after radiation therapy, the tumor has decreased in size, and vision was no longer obstructed. (c) Patient at age 5 years, prior to surgery. (d) Patient at age 10 years, 5 years after surgery. (Permission to publish photographs was granted by the parents.)

 


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  		Figure 1c. (a) Four-month-old patient with hemangioma prior to radiation therapy. Corticosteroid therapy was indicated, and the hemangioma regressed. However, the hemangioma rapidly progressed after corticosteroid therapy was withdrawn. (b) Two months after radiation therapy, the tumor has decreased in size, and vision was no longer obstructed. (c) Patient at age 5 years, prior to surgery. (d) Patient at age 10 years, 5 years after surgery. (Permission to publish photographs was granted by the parents.)

 


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  		Figure 1d. (a) Four-month-old patient with hemangioma prior to radiation therapy. Corticosteroid therapy was indicated, and the hemangioma regressed. However, the hemangioma rapidly progressed after corticosteroid therapy was withdrawn. (b) Two months after radiation therapy, the tumor has decreased in size, and vision was no longer obstructed. (c) Patient at age 5 years, prior to surgery. (d) Patient at age 10 years, 5 years after surgery. (Permission to publish photographs was granted by the parents.)

 
Growth disturbance of the long bones was noted in two patients. In patient 2, a dose of 15 Gy was delivered to the right shin, sparing the long bone, and an additional dose of 12 Gy was delivered to the relapsed hemangioma, including the long bone in the radiation field. The leg was shortened by 5 cm and required surgery. In patient 8, three operations were performed for subluxation of the left hip joint caused by the hemangioma. Because the treatment field was planed to exclude the hip joint, shortening of the left femur by 4.5 cm was caused by surgery.

Limitation of adduction of the right thumb was noted in patient 10. Destruction of the first metacarpal bone by infiltration of the hemangioma was related to this abnormality (Fig 2). There was no other functional morbidity in the irradiated hand in this patient. Slightly hypotrophic muscles were noted in patient 1, who received 10 Gy, and in patient 4, who received 16 Gy. These patients were not concerned about these abnormalities. It is unknown whether these abnormalities were caused by the radiation therapy or by the hemangioma. Severe long-term radiation-related morbidity was noted in only one patient who had required reirradiation because of inadequate size of the treatment field (patient 2).



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  		Figure 2a. (a) Radiograph obtained prior to radiation therapy shows a soft-tissue mass in left palm, associated with infiltration with hemangioma in the first, second, and third metacarpal bones (arrows). (b) Radiograph obtained 3 months after radiation therapy shows that the tumor has decreased in size. (c) Radiograph obtained at age 10 years shows that the tumor has completely regressed, but deformity of first metacarpal bone (arrow) is present.

 


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  		Figure 2b. (a) Radiograph obtained prior to radiation therapy shows a soft-tissue mass in left palm, associated with infiltration with hemangioma in the first, second, and third metacarpal bones (arrows). (b) Radiograph obtained 3 months after radiation therapy shows that the tumor has decreased in size. (c) Radiograph obtained at age 10 years shows that the tumor has completely regressed, but deformity of first metacarpal bone (arrow) is present.

 


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  		Figure 2c. (a) Radiograph obtained prior to radiation therapy shows a soft-tissue mass in left palm, associated with infiltration with hemangioma in the first, second, and third metacarpal bones (arrows). (b) Radiograph obtained 3 months after radiation therapy shows that the tumor has decreased in size. (c) Radiograph obtained at age 10 years shows that the tumor has completely regressed, but deformity of first metacarpal bone (arrow) is present.

 

   DISCUSSION
TOP
 ABSTRACT
 INTRODUCTION
 MATERIALS AND METHODS
 RESULTS
 DISCUSSION
REFERENCES
 
Ninety-five percent of vascular lesions in the skin can be diagnosed with clinical history taking and physical examination (14). Hemangiomas are usually not present at birth but appear shortly after birth as a red macule or telangiectasia. Most pediatric hemangiomas do not cause major problems, but some hemangiomas may grow large and cause various complications, depending on their size and location. These complications, which require rapid attention and treatment, include obstruction of vision, ulceration and bleeding, persistent skeletal and soft-tissue deformity, hemangioma in critical locations, and KMS (14–16).

Hemangiomas that involve the orbit or eyelids can cause obstruction of vision. The incidence of amblyopia with adnexal capillary hemangiomas has been reported (17–19) as 43%–60%. Although hemangiomas invariably regress, they can still cause impairment of limb movement and limb overgrowth due to compression or expansion of surrounding structures. If hemangiomas that cause KMS or those in critical locations are not treated soon enough, they may be fatal.

There is comparatively little information available regarding the long-term results of treatment (20). Isolated cases in which treatment with different modalities was successful have been reported, but to our knowledge, cases in which treatment was unsuccessful have not been reported.

Surgical resection may be used to treat small localized hemangiomas that are not responsive to steroids. However, in large hemangiomas, surgical resection may be technically difficult; these hemangiomas may require serial resection. Some authors (21–23) reported that surgical treatment of giant hemangiomas sometimes leads to consumption coagulopathy.

Corticosteroid therapy is reported to be the first line of pharmacologic therapy for complicated hemangiomas. Many authors (4,17,24–26) confirmed that prednisone (1–3 mg per kilogram of body weight per day) induces regression of skin hemangiomas in 30%–90% of cases after a few hours to 3 weeks of therapy, regardless of the route of administration used. Unfortunately, even if corticosteroids are effective, hemangiomas frequently progress when steroid therapy is discontinued and necessitate multiple courses of therapy (25,27). Side effects of systemic corticosteroid therapy include stunted growth, cushingoid symptoms, and susceptibility to infectious disease (4,14,18).

Therapeutic embolization to occlude the blood supply is another method of management of complicated hemangiomas. Selective arteriography is difficult to perform in infants, whose vessels are short, thin, and prone to arterial spasm and thrombosis. Embolization should be performed only in selected cases and as a temporary measure; an experienced radiologist should perform this procedure (4,21).

Laser therapy has become an indispensable tool for surgery of capillary hemangiomas (14). Pulsed yellow-light lasers providing selective photothermolysis are effective in the treatment of superficial hemangiomas, but they are not indicated for large bulky hemangiomas (28). Use of the Nd:YAG laser, which provides adequate hemostasis in surgical dissection, permits treatment of massive and deep hemangiomas, but it is associated with a high incidence of scarring and delayed healing (17,28).

Radiation therapy was used more widely in the past for hemangiomas before the complications were recognized. The major indication for radiation therapy for hemangiomas in children is for the treatment of lesions with complications that pose a threat to function or life, that fail to improve with corticosteroid treatment, and that cannot be treated with alternative methods. It is also worth noting that the complications arising from the use of corticosteroids can be serious in this population.

Although the use of radiation therapy for hemangiomas has decreased, there are many advocates (14,16,27,29,30) who report that radiation therapy is indicated in certain situations. Radiation therapy is indicated in cases of KMS. El-Dessouky et al (31) reviewed 33 articles and 153 reported cases in the literature and showed that a combination of radiation therapy and steroid therapy produced the greatest reduction in death rate and that surgery alone or corticosteroid therapy alone did not appear to be as beneficial in the treatment of KMS. The mortality rate was 2.5% in patients treated with this combination, 5.7% in patients treated with radiation therapy alone or radiation therapy combined with other modalities, and 30% in patients receiving no treatment (31).

Although the treatment of KMS with radiation therapy has been reported recently, dose-response data are relatively scarce in the literature. Some authors (20,32,33) reported rapid regression of the hemangioma with a concomitant increase in platelet count after a single 3–8-Gy dose of radiation. Others (21,27,31,34) reported the results of a total dose of 7.5–18.4 Gy in five to 16 fractions.

Superficial photons and radioactive implants were used for the treatment of infant hemangiomas until the late 1960s. Fewer cases in which radiation therapy has been used for function-threatening infant hemangiomas have been reported recently (19,27). Plesner-Rasmussen et al (19) described three cases in which hemangioma was treated with radiation therapy and reported that the best cosmetic and functional results were obtained with a dose of 5–10 Gy.

It is important to recognize the risks involved in the use of ionizing radiation in the treatment of benign disease. Fragu et al (11) reported that the risk of dystrophy was 12.1 times higher (P < .001) among patients who received a surface skin dose greater than 30 Gy than among those who received a dose of 10 Gy or less. They also observed basal cell carcinoma of the skin in patients who received more than 10 Gy. Furst et al (12) reported a cancer incidence of 1.46% (224 of 15,336 patients) with hemangiomas that received 5–10 Gy of radium 226 or orthovoltage x-ray therapy, compared with 1.26% (34 of 2,694 patients) with hemangiomas that were not exposed to radiation. The difference was not statistically significant.

Irradiation can cause growth retardation in children (35). Gonzalez and Breur (13) reported that the dose of radiation to the physeal plates was the most important factor in the shortening of the irradiated extremity. When radiation therapy is used to treat life- or function-threatening hemangiomas, the lowest possible dose that produces control of the symptoms should be used, and the dose to adjacent radiosensitive structures must be 10 Gy or less to avoid radiation-induced cancer. Physeal plates should be excluded from the radiation field, but the entire hemangioma might be included in the radiation field in cases of KMS.

In our two patients with KMS, the treatment field was inadequate and required reirradiation or a change of the treatment portal. In five of the other six patients in whom hemangioma regressed and platelet count increased, the dose delivered was 10 Gy or less. Four of five symptomatic patients, with the exception of the patients with KMS, received a dose of 10 Gy or less and had complete regression of the hemangioma with relief of symptoms.

Because of the small size of this study, it is difficult to propose the optimal treatment regimen, but we recently treated patients with KMS with a dose of less than 10 Gy to the entire hemangioma. We believe that radiation therapy is indicated in certain situations of life- or function-threatening infant hemangioma; in these situations, it produces a favorable outcome.


   FOOTNOTES
 
29*. indicates generalized involvement Back

Abbreviation: KMS = Kasabach-Merritt syndrome

Author contributions: Guarantor of integrity of entire study, I.O.; study concepts, I.O., K.T.; study design, I.O., N.A.; definition of intellectual content, I.O.; literature research, I.O., M.H.; clinical studies, I.O.; data acquisition, K.T., S.K.; data analysis, I.O., K.T., H.K.; manuscript preparation, I.O.; manuscript editing, review, and final version approval, all authors.


   REFERENCES
TOP
 ABSTRACT
 INTRODUCTION
 MATERIALS AND METHODS
 RESULTS
 DISCUSSION
 REFERENCES
 

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