Temporary noncicatricial focal alopecia following Gamma knife radiosurgery: Case series and review of literature
Correspondence Address: Source of Support: None, Conflict of Interest: None DOI: 10.4103/0028-3886.241362
Source of Support: None, Conflict of Interest: None
Keywords: Alopecia, epilation, gamma knife radiosurgery, hair loss, radiation therapy
In recent years, gamma knife radiosurgery (GKRS) is being widely used for the management of various benign and malignant intracranial pathologies. Traditionally, GKRS is considered as the safest treatment modality among all other available options, viz. cyber knife radiosurgery, X knife, intensity-modulated radiotherapy (IMRT), and external beam radiotherapy (EBRT), etc. GKRS maintains this safety profile due to its high conformity, precision, and sharp dose fallout, which is better than that seen with any other available options at present. Still, there are chances of collateral damage secondary to factors intrinsic to treatment or patient-related parameters. Alopecia is a well-known complication after conventional whole brain radiotherapy (WBRT). Temporary alopecia following GKRS is a not a properly evaluated complication so far. Here, we discuss our observation with six patients who developed temporary reversible focal alopecia overlying the treated volume after receiving GKRS. All patients consented to the publication of their images.
A 25-year old male patient presented with an arteriovenous malformation (AVM) in the left occipital lobe with evidence of prior intraparenchymal bleed. The lesion was targeted with 21 Gy marginal dose. The patient reported patchy loss of hair over the left occipital area within 10 days of GKRS. The overlying skin was normal with no evidence of erythema, desquamation, or irritative reaction [Figure 1]. The new hair started growing after nearly 25 days of GKRS and the patient gained complete recovery with normal hair by the end of two months.
A 22-year old male patient with a large volume (23.97 cc) AVM in the right frontal area was treated with dose-fractionated GKRS in two fractions (14.5 Gy marginal dose on alternate day schedule in two days). The patient presented after a week with complaint of sudden hair loss over the bifrontal area. By the end of two months, the patient regained new hair over the same area with no further complaint of hair loss or change in the texture/length of hair [Figure 2].
A 62-year old female patient received GKRS for left-sided anterior one-third parasagittal meningioma. The 5.37 cc tumor volume was treated with 17 Gy marginal dose. The patient presented with patchy loss of hair on the scalp exactly overlying the tumor [Figure 3]. The patient regained normal hair in the next 2 months.
A 24-year old male patient received dose-fractionated GKRS for the right-sided large volume glomus jugulare tumor of volume 37.59 cc. The patient presented after 2 weeks with complaint of loss of hair behind and above the left ear [Figure 4]. He regained hair within 2 months (as confirmed on phone). The patient was lost to follow-up.
A 45-year old female patient was treated with 21 Gy marginal dose for a left middle-third parasagittal meningioma. The patient complained of rapid hair loss over a patchy area of the scalp [Figure 5]. The area of hair loss increased over time but at one-and-a-half months of follow-up, the hair on the scalp started regrowing [Figure 5]d.
A 25-year old male patient was treated with 18 Gy dose for a right posterior frontal cavernoma. The patient had patchy loss of hair over the right parietal region which started developing in 2 weeks [Figure 6]. The hair loss was reported just before submission of this series. The patient is in follow-up.
We retrospectively evaluated the treatment plan of all cases. All patients were treated with Leksell Perfexion model (Elekta Instruments, Norcross, GA, USA) with Gamma Plan version 10. The overlying scalp was receiving ≥3 Gy radiation exposure in all the reported cases.
Postradiation epilation is a well-known phenomenon contemporary to the discovery of X-rays in the history. Soon after the introduction of X-rays by Roentgen, Daniel reported radiation-induced epilation in the human scalp in 1896. In the early 20th century, this phenomenon was used therapeutically for X-ray epilation of the face for hirsutism  and tinea capitis , by administering a suberythematous dose of 5–8 Gy (the Kienbock–Adamson technique). The epilation started in 2–3 weeks post radiotherapy and was complete by the end of a month. The new hair began to regrow within 2–3 months. Technical errors, overlapping fields of radiation, and poorly calibrated equipment might have led to permanent cicatricial alopecia.,
Radiosensitivity of the human hair
Hair loss is a well-known phenomenon after the administration of conventional WBRT. Anecdotal case series have reported new-onset local hair loss by one month in nearly 10% of the patients after GKRS. In the line of fire of radiation, the skin and hair get injured as “innocent bystanders.” Hair follicles are one of the most radiosensitive organs of the body. In its life-time, a hair passes through three different phases – telogen (resting phase), anagen (growth phase), and catagen (regression phase). At a given point of time, approximately 90% of the hair follicles are in the anagen phase. Hair in the anagen phase are much more sensitive to radiation than those in the telogen phase [Table 1].,,
Gamma knife exerts its genotoxicity-induced cell death by causing deoxyribose nucleic acid (DNA) damage by administration of the high-dose ionizing radiation. The mechanism of radiation-induced alopecia has been well recognized for more than a century but there has not been any effective measure to prevent it. The high radiation sensitivity of an anagen follicle is responsible for radiation-induced epilation. It has been reported even after embolization of cerebral arteriovenous malformations secondary to radiation exposure during the endovascular procedure. The regenerative capacity, the time frame of alopecia to develop, and the mechanism of regeneration still remain poorly understood. Various hypotheses have been proposed for the mechanism of regeneration of hair follicles after RT (e.g., activation of mammalian target of rapamycin complex 1 [mTORC1] signaling), but they do not explain the occurrence of different patterns of alopecia and the differential effects of various radiation modalities.,,,
3 Gy exposure and hair loss
Post-radiation alopecia is a dose-dependent phenomenon that can be temporary or permanent. One important phenomenon is focal alopecia that is devoid of any inflammatory signs over the overlying scalp. It is seldom difficult to prevent 3 Gy exposure to the scalp while treating superficial located lesions with a high-dose, single-fraction radiosurgery. The radiation exposure of ≥3 Gy leads to loss of transit amplifying cells (TAC) in the dystrophic hair (anagen effluvium), followed by telogen shedding due to the premature catagen entry of hair follicle in the late anagen phase. A 3 Gy exposure produces complete reversible anagen alopecia, whereas permanent alopecia starts at 5 Gy exposure., After a radiation exposure of up to 3 Gy, patients usually recover from “anagen arrest” but a higher radiation exposure in the range of 5 Gy may lead to permanent destruction of hair follicles. Williams et al., observed that depilated hair were pointed in configuration. The hair that did not fall after radiotherapy and continued to grow had a markedly constricted shaft. Complete hair growth is expected to occur after 2–4 months of irradiation in the reversible type of radiation-induced alopecia. A few investigators have advocated volumetric arc therapy-whole brain radiotherapy (VMAT-WBRT) for reducing radiation exposure to the dermis and the cutaneous appendages to an extent of 20.5%.
The area of temporary alopecia seen in our patients was the part of the scalp closest to the tumor and received a high enough radiation dose to injure the cutaneous appendage. In comparison to the sparse alopecia observed with conventional radiotherapy, focal alopecia after GKRS shows a sharp margin between the hairy and the alopecia zone. It can be concluded that such an exposure in a single setting does not even spare the hair in telogen phase.
Role of primary pathology in the distribution of hair loss
The location of primary pathology is a determining predictive factor for alopecia. Most of the anagen follicle lie at the depth of 4–5 mm in the scalp. The radiosurgeon can control radiation spillage to the scalp by choosing a better conformal plan (by minimizing 3 Gy exposure to the scalp). However, it should be weighed with the risk–benefit analysis for an individual patient. Frequently, a higher differential radiation dose is prescribed for the lesions at the surface; or larger shots are placed at the periphery of the lesion, e.g., a perpetual dose spillage is allowed over the dura and the adjoining bone in convexity/parasagittal meningiomas to control vascularity. Similarly, a high radiation spillage is noted with dural arteriovenous fistulae or arteriovenous malformations situated at the cortical surface. The authors believe that this complication is dependent on the location of the tumor rather than on its histopathology. However, temporary reversible alopecia should not be a negative predictive factor in deciding an optimal dose and plan for effectual treatment of the primary lesion.
Why is hair loss reversible after gamma knife therapy?
The hair loss after radiotherapy is usually reversible. The hair loss starts approximately 2–3 weeks after starting radiotherapy. The new hair start growing again after 2–3 months once the treatment is over. The regenerative phase of cell replacement characterized by a sharply increased cell replication rate is observed from the 3rd to 5th post-radiation weeks. Complete hair regrowth generally occurs by 2–4 months after RT. The new hair might be different in texture, strength, and color from the previous hair. In their study on mice models, Wang et al., have found that maintaining the transient amplifying cell (TAC) population after irradiation may help to reduce hair loss after RT. In physiological situations, mTORC1 signaling is needed for the activation of hair follicle stem cells in the telogen-to-anagen phase transition.,
A higher dose irradiation leads to dermal fibrosis and clinical scarring of the skin. Histopathological evaluation of such cases dictates the candidature of such a patient for hair transplantation in a setting of irreversible alopecia. Hair transplantation remains a viable option in patients without any dermal fibrosis. All our patients had an average hair density except for a focal alopecia over the irradiated area. There was complete alopecia over that area with a sharp hair density change from the periphery of the irradiated zone. The overlying skin was neither infective nor fibrotic, or with any inflammatory changes. Judging by the temporal sequence of hair recovery in all patients, we did not feel any need for biopsy from the zone of alopecia. Some authors have performed punch biopsy from the alopecia zone and compared it with the uninvolved site after conventional radiotherapy. Historically, some cases have demonstrated thinning of the dermis, a decreased number of follicular units, damaged adnexal structures, miniaturized anagen follicles, fewer acini per gland, focal hyalinization of the basement membrane, and/or intact subcutaneous fat following WBRT.
Can there be a separate pathophysiology of hair loss after gamma knife radiosurgery when compared to conventional radiotherapy
The radiobiology of GKRS is entirely different from the radiobiology of conventional radiotherapy. The effect of radiation therapy is different on the skin and its appendages depending on the wavelength, cumulative dose, dose per fraction, and energy of the beam. In their landmark article, Borak et al., earlier defined the lethal dose for different structures; 12 Gy for the sebaceous gland, 16 Gy for the hair follicle, 20 Gy for the epidermis, and 25 Gy for the the sweat glands. In contrast to the conventional radiotherapy, such a high dose is not expected with GKRS owing to a sharp dose fallout outside the targeted volume. A high radiation tolerance of the scalp vasculature and the absence of any dermatitis, erythema, desquamation, or long-term sequel in any of our patients practically rules out the chances of any radiation-induced vascular injury. Chronic dermatitis, a dry skin, and a change in quality as well as the length of hair have been described after conventional RT (6 months to 1 year). The other important denominator resulting in lesser side effects with GKRS and cyberknife is the presence of a megavoltage radiation source, which spares the skin while targeting the deeper targets inside the brain.
The patient's perspective on hair loss
Hair is an integral part of a person's beauty, a matter of self-esteem, and a major cause of apprehension while undergoing radiotherapy. Loss of hair can be responsible for significant psychological trouble and a reduced quality of life. It becomes especially important for the patients in a business where the appearance of the patient affects the outcome, e.g., actors, artists, etc. For some patients with a poor overall survival (e.g., those with an intracranial metastasis), the time frame for regrowth of hair often exceeds the life expectancy of the patient. Hence, hair sparing radiotherapy techniques should be practiced to gain scores in the quality of life. A patient usually becomes anxious due to the sudden patchy loss of hair and seeks consultation for the same. With the pattern of hair loss observed by the authors, we believe that the information regarding the occurrence of this possible complication should be conveyed to the patient before the conduction of the procedure. The patient should also be told that, in the majority of the cases, the alopecia is focal and usually manifests in a location overlying the treated volume. It should be stressed that alopecia is reversible and noncicatricial with complete recovery of hair occurring in a 2–3 month period, and no further measures need to be taken apart from a careful observation. The patient should be advised to avoid hair dryers/blowers, curling irons, clips, hair sprays, curling hairs, hairbands, etc. One should not practice vigorous massage after application of hair oil, and the hair should be patted dry with a soft towel after the bath. On a precautionary note, the exposed part of the scalp should be covered with any scarf or hat to protect it from the sun's rays, or from cold or sudden temperature change. Some authors have suggested the use of nitroxidetempol and tempo, vitamin D3, and 16,16 dimethylprostaglandin E2 (PGE2) prior to radiation to mitigate the chances of post radiation alopecia. No patient in our series needed hair transplantation.
After evaluating these patients, the authors believe that there might be many more patients who either do not report their hair loss, or suffer from subclinical hair loss after stereotactic radiosurgery. In the past, we did not perform a thorough investigation of this complication due to our ignorance regarding the occurrence of the complication. Another limitation of this study was the absence of histopathological correlation and textural analysis of regrown hair after the period of alopecia. A prospective trial can be conducted for patients routinely receiving stereotactic radiosurgery for superficially located pathologies with dose spillage (≥3 Gy) to the scalp; and, alopecia scoring can be performed on the “global alopecia areata severity scoring scale” for an objective assessment of the hair loss. The dose–effect relationship for temporary alopecia is poorly investigated, and the available literature gives details of this complication only in patients who have received WBRT. Two of our patients received dose-fractionated GKRS on alternate days; it gets further difficult to calculate the built up doses in such patients at the dermis, as well as the volume of radiation dose delivered to the hair follicle. Another limitation was our lack of assessment of the possible radiation exposure during digital subtraction angiography in two patients of AVM, which might have contributed to the additional radiation exposure. With the growing popularity of the newer models for the delivery of stereotactic radiosurgery (e.g., the Leksell ICON model), fractionation is becoming a norm for selected patients, and the effects of this form of treatment on the development of alopecia also needs to be evaluated.
Declaration of patient consent
The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.
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Conflicts of interest
There are no conflicts of interest.
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