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1 Scoring Systems for Radiation-Induced Skin Reactions

1 Scoring Systems for Radiation-Induced Skin Reactions

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B. Fowble et al.


Table 3.1 Standard scoring systems for acute and late radiation skin toxicity

CTCAE v4.0 [3]

Toxicity Acute



No change


Faint erythema

Dry desquamation





Moderate-brisk erythema

Patchy moist desquamation in skin folds and creases

Moderate edema

Moist desquamation other than skin folds

Bleeding with minor trauma

Skin necrosis or ulceration

Spontaneous bleeding

Skin graft needed


10-question survey applicable to a variety of

different skin conditions and has been used in the

context of evaluating the impact of dermatologic

treatments and targeted therapies.

For quality of life impact of targeted therapies, major available patient-reported instruments include the FACT-EGFRI-18 [15], an

18-question survey that assesses the physical,

emotional, social, and functional impact of the

skin, nail, and hair toxicities from EGFRinhibition therapy, and the hand-foot syndrome 14 (HFS-14), a 14-item questionnaire for

patients experiencing chemotherapy-associated

hand-foot syndrome and hand-foot skin

reaction [16].

Radiation-related skin reactions vary in frequency, intensity, and severity. Factors which

influence the observed reactions are divided

into patient and treatment related. Patientrelated factors include the anatomic site, sex,

body mass index, age, ethnicity, sun-reactive

skin type, bra or breast size, comorbidities

including collagen vascular disease and HIV,

smoking, and genetic mutations [6, 7, 17–30].

Treatment-related factors include the expanse

of the skin within the treatment field, the beam

energy, total dose and fractionation, the use of

RTOG [1]




No change

Faint or dull erythema

Dry desquamation

Follicular reaction


Decreased sweating

Tender or bright erythema

Patchy moist desquamation

Moderate edema

Confluent moist desquamation

other than skin folds

Pitting edema

Ulceration, hemorrhage


No change

Minor symptoms

No treatment

Death related to treatment

Moderate symptoms



Severe symptoms

Aggressive treatment

Irreversible damage

Major intervention

Death or loss organ

bolus and its frequency, the use of tangential

beams, intensity-modulated radiation, the use

of radiosensitizers, chemotherapy, and targeted

agents [19, 25, 31–41].

The characterization of the skin reaction

differs among the scoring systems as noted in

Table 3.1. Interobserver variability is a common

challenge. Below we provide descriptions and

photographic examples of acute and late skin

reactions. The examples highlight the spectrum

of changes that may be seen.


Acute Reactions



While the initial reaction to radiation therapy

occurs as early as the first treatment, the earliest

visible manifestation of a radiation-related skin

reaction is erythema. It typically occurs in the

second to third week of treatment and initially

appears as a slight pink discoloration. It may

progress to a bright red or reddish purple color as

the cumulative dose increases. It can be described

as mild, moderate (brisk), or marked. It is a result

of the destruction of the basal cells with an


Types of Radiation-Related Skin Reactions

inflammatory response characterized by erythrocyte extravasation and capillary dilatation in the

dermis (Table 3.2).



Erythema may be accompanied by hyperpigmentation especially in African-American patients or

patients of other ethnicities with darker skin

pigment. The hyperpigmentation often involves

the nipple/areolar complex in women with breast

cancer and may persist for several months following completion of treatment (Table 3.3).


Dry Desquamation

Dry desquamation typically occurs at doses of

3000 cGy or higher. It is characterized by shedding of the outer layers of the skin as new cells

migrate to replace the damaged cells (Table 3.4).


Moist Desquamation

Moist desquamation occurs when the epidermis

sloughs and the underlying surface are moist and

edematous. Epidermal loss may increase the risk

of infection and moist desquamation may be associated with purulent exudate. Moist desquamation

occurs at doses above 4000 cGy and is most likely

to occur in skin folds where there is self-bolus.

Reepithelialization should occur within 10–14

days of the onset of moist desquamation and is

characterized by the appearance of islands of new

skin cells which are white in color and should not

be confused with infection (Table 3.5).




Cutaneous Candidiasis

Cutaneous candidiasis may develop in moist

areas such as the groin, axilla, or inframammary

fold region of the breast. It has a characteristic

appearance of areas of erythema with plaque

like lesions with peripheral scaling. Papules and

pustules may be present. These changes should

not be mistaken for erythema related to radiation. A topical antifungal should be added to the

skin care regimen for areas of suspected candidiasis (Fig. 3.1)


Late Reactions


Pigmentation Changes

Reepithelialization in areas of moist desquamation may result in hypopigmentation or hyperpigmentation of the skin or a combination of the

two. A change in pigmentation is most often seen

in African-American patients. Hypopigmentation

of the nipple/areolar complex is also seen in some

Caucasian women. The acute hyperpigmentation

seen in African-American patients may not

resolve completely, leaving the treated area

hyperpigmented for long periods or even permanently (Table 3.7).



Telangiectasias are dilated superficial blood vessels. Their incidence is increased in areas of prior

moist desquamation. They are permanent and

tend to increase with time. They can be removed

with laser therapy but generally require multiple

sessions and may reappear (Fig. 3.2).



Folliculitis is an infection of the hair follicles which

is characterized by the appearance of multiple

small erythematous lesions that are raised and pruritic. Purulent material (pustule) may be present in

the center of the lesions. The infectious agent

is usually Staphylococcus aureus. Management

includes the use of topical agents (Table 3.6).


Edema is characterized by persistent interstitial

swelling of the tissues. It is more common in

areas of dependency (extremities, pendulous

breast) and may be chronic in nature. In breast

cancer it has been reported to peak at 3–6 months

with resolution by 3 years (Table 3.8) [7].

B. Fowble et al.


Table 3.2 Erythema

Mild erythema

Week 2, bilateral breast cancer,

reduction mammoplasty,

beginning of mild erythema

Moderate erythema

Week 4, moderate erythema,

right breast whole breast

radiation, breast-conserving


Week 4, IMRT, adenocarcinoma

of the left lung, posterior thoracic


Week 4, sarcoma treated to right

proximal medial thigh

Week 3, breast-conserving


Marked erythema

Week 5, bilateral breast cancer,

reduction mammoplasty, marked


Week 5, reconstructed breast

with transverse upper gracilis

microvascular flap. Custom bolus

every other day

Week 6, cancer, base of tongue

Week 5, cancer of the pyriform



Types of Radiation-Related Skin Reactions


Table 3.3 Hyperpigmentation

6 weeks postradiation. Filipino,

total nipple skin sparing

mastectomy, custom bolus every

other day

Week 6. Hispanic male, sarcoma,


6 months postradiation, Indian

female with locally recurrent

inflammatory breast cancer,

TRAM flap. Bolus daily with

concurrent Xeloda and chest wall


3 weeks postradiation. Resolving

hyperpigmentation. Breastconserving surgery, AfricanAmerican female

1 week postradiation, Ewing’s

sarcoma, dry desquamation in the

clavicular region

Table 3.4 Dry desquamation

2 weeks postradiation, squamous cell carcinoma of the

left lower lip, concurrent cetuximab. Exhibits dry

desquamation in surrounding neck

2 weeks postradiation, dry

desquamation, intact breast


B. Fowble et al.



Types of Radiation-Related Skin Reactions

Table 3.5 Moist desquamation

Moist desquamation

Diffuse moist desquamation

1 week postradiation, focal moist desquamation,

inframammary fold, without exudate

1 week postradiation, chest wall recurrence, implantreconstructed breast

2 weeks postradiation, concurrent weekly cisplatin,

focal moist desquamation; cancer, base of tongue

2 weeks postradiation; concurrent cisplatin, squamous

cell carcinoma, left oral tongue; diffuse moist



B. Fowble et al.


Table 3.5 (continued)

Moist desquamation

Diffuse moist desquamation

Week 4, post-squamous cell carcinoma of the upper

esophagus, status post endoscopic mucosal resection

and subsequent hiatal esophagectomy for multifocal

dysplasia throughout esophagus. Recurrence in the right

supraclavicular node, level 3 and paratracheal areas.

Radiation with concurrent carboplatin and Taxol, moist

desquamation with purulent exudate

Week 6, squamous cell carcinoma of the perianal

region, perineum with diffuse moist desquamation.

Treated with IMRT and concurrent 5-FU and

mitomycin C

African-American male, anal cancer, IMRT with

concurrent 5-FU, and mitomycin C. Perineum with

moist desquamation and beginning reepithelialization

(white patches)


Types of Radiation-Related Skin Reactions


Table 3.5 (continued)

Moist desquamation

Diffuse moist desquamation

2.5 weeks postradiation; Ewing’s sarcoma,

desquamation, and beginning epithelization

Table 3.6 Folliculitis

Week 4, intact breast with central

area of folliculitis

1 week postradiation, breast with

wide area of folliculitis

Week 6, reconstructed breast with

areas of folliculitis, upper inner

quadrant and inframammary fold


Fig. 3.1 Breast cancer; development of cutaneous candidiasis along incision site that had been sealed with glue


Radiation fibrosis results in loss of parenchymal

cells with the increased formation of fibrous tissue. In the skin and soft tissues, the affected

area(s) becomes firmer and tighter and at times

painful. It is correlated with total radiation dose,

the volume(s) treated [42, 43], and overlapping

fields [44]. The changes have been thought to be

irreversible, but preclinical models and limited

success with clinical interventions suggest some

degree of reversibility (Fig. 3.3) [44–46].

B. Fowble et al.


Table 3.7 Pigmentation changes

5 weeks postradiation, concurrent cisplatin, left oral

tongue cancer

2 week break between weeks 5 and 6 of treatment.

African-American male, anal cancer, hypopigmentation

during second week of 2-week break


Fig. 3.2 5.5 years postradiation. Intact breast with

telangiectasia inframammary fold. Status post-breastconserving surgery


Morphea is a localized form of scleroderma.

It is characterized by circumscribed patches

or plaques of sclerosis with induration. The

areas may be erythematous or hypopigmented.

Radiation-induced morphea has been reported

in women with breast cancer treated with

breast-conserving surgery and whole breast

radiation [47–49] or partial breast radiation

[50]. The changes may appear outside of the

area of radiation [49]. It is reported to occur in

1/500 women treated for breast cancer [51, 52].

The interval from radiation to the appearance of

morphea ranges from 1 month to 32 years [51,

53, 54]. It is not a precursor to systemic sclerosis. It should not be confused with a recall reaction (Table 3.9).



Types of Radiation-Related Skin Reactions

Table 3.8 Edema

5 weeks postradiation, concurrent cisplatin upper neck

edema related to surgery and radiation

4 months postradiation. Breast edema

Fig. 3.3 Week 3, recurrent

pleomorphic undifferentiated sarcoma with invasion

into the tibia, fibrosis of the

anterior tibia. Status postresection and IORT 15 Gy

B. Fowble et al.


Table 3.9 Morphea

2 years postradiation. Breast


radiation-induced morphea

Photo courtesy of M. Kari

Connolly, MD

Radiation-induced morphea

presenting 7 months posttreatment.

70-year-old female with pT2N0

luminal A cancer s/p lumpectomy

and radiation

Photos courtesy of Jyoti Mayadev,


Table 3.10 Recall skin reactions

9 months postradiation; recall reaction related to

doxorubicin, with erythema in breast and supraclavicular


Postmastectomy radiation for chest wall recurrence with

recall reaction; moist desquamation following liposomal

doxorubicin transarterial chemoembolization for

hepatocellular cancer

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