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4 Other Factors Affecting Acute Skin Toxicity

4 Other Factors Affecting Acute Skin Toxicity

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S.S. Yom and F. Yuen



84



Targeted therapies (such as erlotinib) have

been very rarely used with SRT. The one

prospective trial that has been published did not

report dermatologic or chest wall toxicity [43].



6.4.3



Reirradiation



For patients being reirradiated to the chest for palliative purposes, skin reaction has not been reported

as a dose-limiting toxicity [44]. However, patients

who have been previously radiated to the thorax

and are treated again with curative intent can be at

higher risk for radiation skin toxicity, especially if

the second treatment is given with stereotactic

technique. One study of this specific clinical scenario reported an incidence of grade 2 or higher

chest wall pain in 18 % and skin toxicity in 5 %

[45]. For these patients, the original plan should be

reviewed, and consideration should be given to

avoid excessive skin and chest wall dosages to

areas treated previously. Particular attention should

be paid if the reirradiation will include the supraclavicular region or neck. For these cases, thermoluminescent dosimetry is advised to gauge the

delivered dose to the areas at highest risk.



6.5



Management of Skin

Reaction



Most thoracic radiation patients will not require

very extensive management. Ongoing self-care

activities should be encouraged to minimize the

reaction and not allow it to progress. Most of the

time, the program will require relatively simple

interventions such as moisturization to relieve dryness as well as consideration of light cotton clothing

or dressings (Mepilex Lite) to reduce friction and

sun exposure to the area. Itching is an issue that

should be very actively managed; if the patient

scratches the area, there is increased irritation and

exacerbation of the reaction, with risk for dry desquamation as well as infection. These patients

should be given soothing emollients, 1 % topical

hydrocortisone lotion, and if the reaction is truly

very severe, antipruritic medication can be prescribed or intermediate potency steroid creams may

be required. All patients should be generally coun-



seled to avoid sun exposure to the chest area, and, if

swimming is desired, moisturization is advised after

completion of activity (a partner may be needed to

help apply the moisturizer over the back, where tanning is typically the most pronounced).

For patients who experience severe brisk erythema, cooling hydrogels should be used to increase

comfort. The rare patients who demonstrate a very

intense level of this reaction are at high risk for wet

desquamation and should be monitored closely. For

severe wet desquamation, control of potential skin

infection may be required. In our clinic, we will

consider the use of silver-containing amorphous

hydrogel (Silvasorb) or, in very severe cases, silverimpregnated hydrofiber or alginate dressings.



6.6



Photographs

and Recommendations



Below are general skin care recommendations

(Table 6.1), week-by-week treatment instructions,

and photographs that demonstrate typical skin reactions over time for patients undergoing external

beam radiation to the thorax (Table 6.2). Photographs

of special reactions and instructions on how to treat

these more uncommon cases are also provided

(Table 6.3). Figure 6.1 is a general suggested treatment algorithm for skin care for patients undergoing external beam radiation to the thorax.

Table 6.1 General principles of skin care for patients

with skin reactions involving the thorax

Patient should:

• Cleanse daily with mild soap and water

• Use lotions and creams recommended by your

provider

• Continue to wear soft under garments that

provide support and control moisture

Patient should not:

• Rub, put pressure on, or scratch radiated area

• Take hot water showers, hot baths, use wash

cloths, or use loofahs

• Apply any lotion, cream, or ointment within the

3 hours prior to radiation treatment

• Wash off lotion, cream, or ointments if applied

three or more hours before radiation treatment

• Apply drying agents to the skin unless instructed

to do so

• Use any tape or adhesives on the radiated skin



6



Thoracic Cancers



85



Table 6.2 Examples of typical acute skin reactions and recommended interventions for patients undergoing external

beam radiation to the thorax

Week

1–2



Skin reaction

Caucasian male lung cancer

patient receiving IMRT to a

dose of 45 Gy in 25 fractions

with a reaction on the thorax



Reaction type

Development of mild

hyperpigmentation



Intervention

• Cleanse daily with mild

soap and water

• Apply Lotion Soft twice a

day



3



Hyperpigmentation and onset

of mild erythema







4



Mild erythema







Cleanse daily with mild

soap and water

• Apply Lotion Soft twice a

day



Cleanse daily with mild

soap and water

• Apply calendula twice a

day



(continued)



S.S. Yom and F. Yuen



86

Table 6.2 (continued)

Week

5



Skin reaction



Reaction type

Mild to moderate erythema



Intervention

• Cleanse daily with mild

soap and water

• Apply calendula twice a

day

• Apply A&D Ointment or

Aquaphor before bedtime



1



78-year-old male with newly

diagnosed metastatic prostate

cancer with a thoracic spine

vertebral metastasis s/p

resection and stabilization,

followed by postoperative

radiotherapy with 3000 cGy

in 10 daily fractions



No reaction







No reaction







2



Cleanse daily with mild

soap and water

• Apply Lotion Soft twice a

day



Continue to cleanse daily

with mild soap and water

• Apply Lotion Soft twice a

day for 1 week post XRT,

then as needed



6



87



Thoracic Cancers



Table 6.3 Special cases and reactions

Description

Primary adenocarcinoma lung

cancer stage IIIB treated with

carboplatin, paclitaxel, and

cetuximab



Reaction type

Cetuximab-induced paronychia



Treatment and intervention

• This side effect may occur in

10–15 % of patients, especially

those treated for longer than 2

months

• It is painful and results in

functional impairment

• Prevention should include

frequent inspection, gentle

cleansing, moisturization, and

avoidance of trauma

• Treatment requires topical

antiseptics and oral antibiotics



62-year-old male with

adenocarcinoma of the superior

sulcus, treated 3.5 years earlier

with 15 Gy of 3D conformal

external beam radiotherapy and

15 Gy of neutron therapy



Hyperpigmentation, fibrosis, atrophy,

and plexopathy









Stage IIIA adenocarcinoma at

45 Gy/25 fx preoperative

radiation treatment, with

carboplatin/paclitaxel



Example of reaction at the thoracic

inlet/low neck



Cleanse with mild soap and water

Moisturize daily following bath



(continued)



S.S. Yom and F. Yuen



88

Table 6.3 (continued)

Description

Asian patient with stage IIIB

adenocarcinoma being treated to

high dose for curative intent, with

involved nodes in the

supraclavicular region, receiving

definitive concurrent

chemoradiation (60 Gy)



Reaction type

Example of mid-neck reaction,

moderate/marked erythema



Treatment and intervention

• Cleanse with soap and water or

Skintegrity and moisturize twice

daily with calendula or Aquaphor

• Mepilex Lite for comfort as

needed



Stage IIB cavitary squamous cell

carcinoma at 50 Gy



While most patients will develop

reactions of erythema, dryness,

freckling, and tanning on the back,

occasionally patients will develop skin

reactions anteriorly as well







Cleanse with soap and water or

Skintegrity and moisturize twice

daily with calendula or Aquaphor



6



Thoracic Cancers



89



Fig. 6.1 Suggested treatment algorithm for skin care



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7



Breast Cancer

Barbara Fowble, Catherine Park,

and Florence Yuen



Breast cancer is the most common cancer in

women. It is estimated that 231,840 women in the

United States will be diagnosed with breast cancer

in 2015 [1]. Radiation is an integral component of

the treatment of early-stage breast cancer and in the

majority of women is administered after breastconserving surgery. However, recent studies have

reported increased trends for mastectomy with or

without reconstruction [2, 3]. Postmastectomy

radiation is received by almost 80 % of women

with established indications for treatment and 47 %

of those with weaker indications [4]. Radiation

may also be used to palliate sites of metastatic disease such as the lung, bone, or brain. Inoperable

locally advanced tumors may benefit from radiation with a resultant decrease in bleeding, ulceration, drainage, and odor and in some cases may be

rendered operable.



7.1



Types and Frequency of Skin

Reactions



The majority of the literature on the prevention

and treatment of acute radiation dermatitis has

focused on breast cancer patients. Radiation

dermatitis is common in these women and

B. Fowble, MD, FACR, FASTRO (*) • C. Park, MD

F. Yuen, RN, MSN, AOCNP

Department of Radiation Oncology, University of

California, San Francisco, 1600 Divisadero, H1031,

San Francisco, CA 94115, USA

e-mail: BFowble@radonc.ucsf.edu



ranges from mild erythema which occurs in

90–95 % to brisk erythema with or without

moist desquamation and dry desquamation [5].

The skin reaction increases throughout treatment as the dose is cumulative. The peak reaction occurs 1–2 weeks post treatment [6–8].

Therefore, studies which evaluate skin toxicity

at 6 weeks post treatment will underestimate

the maximum acute reaction. The effectiveness

of an intervention will vary with the treatment

interval at which it is tested. Some interventions may be effective earlier in the treatment

but not later as the reaction peaks.

Modifications of the Radiation Therapy

Oncology Group (RTOG) [9] and Common

Terminology Criteria for Adverse Event (CTCAE)

[10] skin toxicity scoring systems have been proposed to better reflect the changes observed in

breast cancer patients [11–13]. Moist desquamation

is the most clinically significant skin reaction in

women with breast cancer. However, in the RTOG

and CTCAE scoring systems, moist desquamation

in the inframammary fold is classified as a grade 2

toxicity. Wright et al. [13] added three subcategories to grade 2 toxicity of the CTCAE scale. The

authors recommended the use of the following

scores: grade 1 (faint or dull erythema and/or follicular reaction and/or itching), grade 2 (bright erythema and/or tender to touch), grade 3 (dry

desquamation with or without erythema), grade 4

(small or moderate moist desquamation), grade 5

(confluent moist), and grade 6 (ulceration, hemorrhage, or necrosis).



© Springer International Publishing Switzerland 2016

B. Fowble et al. (eds.), Skin Care in Radiation Oncology, DOI 10.1007/978-3-319-31460-0_7



93



B. Fowble et al.



94



Table 7.1 [5, 6, 12–24] presents series reporting acute skin toxicity in breast cancer patients

receiving radiation. The incidence of grade 2–3

toxicity ranges from 23 to 80 % with the incidence

of moist desquamation ranging from 15 to 48 %.

This variation reflects the type of surgery (breastconserving surgery vs. mastectomy) and the

extent of moist desquamation (any moist desquamation vs. extensive). Bolus is often used on the

skin surface to increase dose in the postmastectomy setting. In the absence of bolus, TLD (thermoluminescent dosimeter) measurements for

surface dose are similar for the intact breast

(inframammary fold) and mastectomy patients



(inferior lateral) and average 3400–3900 cGy for

conventional fractionation [14] with 6 or 6/18 MV

photon tangential beams. With the use of bolus,

Graham et al. [21] recorded TLD surface dose

measurements of 203–215 cGy per fraction.

Breast edema has been reported to be present

in 5–20 % of women before the initiation of

radiation [5, 15, 25]. It has been correlated with

the extent of the surgical resection and axillary

surgery (axillary dissection vs. sentinel node

biopsy) and post-surgery edema and infection

[15]. Freedman et al. [25] reported that with

IMRT it peaks 3–6 months after treatment and

generally resolves within 3 years. At 3–6



Table 7.1 Acute skin toxicity; breast cancer

Number

Study

of patients

Breast-conserving surgery

RTOG 9713 [14] 172

804

Freedman [12]



Fractionation



Technique



Conventional

Conventional



2D

Wedgebased

IMRT

Wedgebased

IMRT

Not stated

3D

IMRT

IMRT

Wedgebased vs.

IMRT

Wedgebased vs.

IMRT



Pignol [5]



331



Conventional



Back [15]

Rutter [16]

Freedman [17]

De Langhe [18]

McDonald [19]



223

69

75

377

240



Conventional

Conventional

Hypofractionated

Hypofractionated

Conventional



Harsolia [20]



172



Conventional



Postmastectomy

Graham, PH [21]

Pignol [6]

Wright [13]

Ma [22]

Spierer [23]

Cuaron [24]



318

257

110

85

118

26



Not stated

Conventional

Conventional

Conventional

Conventional

Conventional



Not stated

3D

3D

IMRT

Electrons

Protons



Toxicity

GR 2–3

(%)



Toxicity

GR 3 (%)



Moist

desquamation (%)



37

75

52



RTOG

CTCAE



23

58

52

39

85

41



80

42



Scoring

system



48

31



CTCAE



31

33



RTOG

[none]

CTCAE

CTCAE

RTOG



15



6

1



41

33

8



CTCAE



28

41



52

29



CTCAE

CTCAE

CTCAE

CTCAE

RTOG

CTCAE



CTCAE common terminology criteria for adverse events, 2D two dimensional, 3D three dimensional conformal, IMRT

intensity-modulated radiation therapy



7



Breast Cancer



months, 26 % of women were noted to have

breast edema. At 3 years 3.7 % had persistent

breast edema. Vicini et al. [26] reported a 54 %

incidence of breast edema in African-American

women compared to 43 % in Caucasian women.

A systematic review of breast edema following

breast-conserving surgery and radiation reported

significant variation in the incidence of breast

edema (0–90 %) depending on the method of

assessment (patient, physician, imaging) [27].

Factors which contributed to the incidence of

breast edema include larger breast size or separation, higher boost dose and larger boost volume, conventional wedge-based tangents, and a

shorter interval between intraoperative radiation

and external beam radiation [27]. Harsolia et al.

[20] reported chronic breast edema in 25 % of

large breasted women treated with wedge-based

radiation compared to 1 % for those treated with

IMRT. The influence of systemic therapy on

breast edema has varied. Some studies have

reported an increased incidence of breast edema

with chemotherapy [25, 28], while others have

not [29]. Tamoxifen has been associated with an

increased incidence of breast edema [29, 30].

However, the incidence of breast edema has not

been influenced by whether tamoxifen was

given concurrently or sequentially with radiation [31].



7.2



Factors Affecting Acute Skin

Toxicity



7.2.1



Intact Breast



Patient-related factors that have been associated

with increased acute skin reactions include higher

body mass index (BMI), larger bra cup size, and

smoking [5, 8, 12, 14–16, 18, 25, 32]. The

increased acute skin reactions observed in larger

breasted women have been attributed to dose

inhomogeneity and self-bolus in the axilla and

inframammary fold region [33].

There have been no studies to date which have

examined differences in acute skin toxicity based

on race in women treated with breast-conserving

surgery and radiation. Two studies have reported



95



worse cosmesis in African-American women

[26, 34], while one has not [35]. None of these

studies commented on acute reactions. Ulff et al.

[36] reported a more pronounced acute dermatitis

in patients with fair or Fitzpatrick type 1 skin

[37]. However, Herst et al. [38] found no association between Fitzpatrick skin type and the incidence of moist desquamation.

The role of common genetic variants (single

nucleotide polymorphisms) in predicting acute

radiation skin reactions has been the focus of

several recent studies in breast cancer patients.

De Langhe et al. [18] reported increased acute

skin toxicity in women with a genetic variation

in MLH1 rs1800734. Acute radiation dermatitis

has not been associated with SNPs in the DNA

repair genes of XRCC1, APE1, and XPD [39] or

polymorphisms in the TP53 or p21 genes [40].

ATM SNPs have more commonly been associated with late toxicity [41–44]. However,

Iannuzzi et al. [43] also reported an increased

incidence of ATM mutations in women who

developed moist desquamation. To date there

has been no correlation with BRCA 1/2 mutations and acute radiation skin toxicity in breast

cancer patients [45–48].

Treatment-related factors that have diminished the frequency of grade 2 or higher acute

skin reactions include the use of intensitymodulated radiation therapy (IMRT) [5, 12, 18,

25], the use of higher energy photons [5], the

prone position [18, 49], and the use of moderately hypofractionated regimens [50–54].

The use of antiperspirants and deodorants during breast cancer radiation in the past was contraindicated due to concern for a possible bolus or

irritant effect resulting in increased axillary acute

skin toxicity. Five randomized trials have now

demonstrated that the use of nonaluminum- [55–

57] and aluminum-containing deodorants [58, 59]

does not increase acute axillary skin reactions with

conventionally or hypofractionated regimens.

Guidelines developed by the Oncology Nursing

Society [60] for the treatment and prevention of

radiation dermatitis include allowing patients to

use nonaluminum-based deodorants during treatment. The recommendation can now include the

use of aluminum-containing antiperspirants.



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4 Other Factors Affecting Acute Skin Toxicity

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