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1 Types and Frequency of Skin Reactions

1 Types and Frequency of Skin Reactions

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NR



Chemotherapy:

NCI CTC v 2.0,

RT: RTOG criteria



Acute: NCI CTC v

2.0, Late: RTOG

criteria



Acute: NCI CTC v

2.0, Late: RTOG/

EORTC criteria

NCI CTCAE v 3



Surgical Resection

Followed by Radiation

vs. Concurrent

Chemoradiation



Concurrent

Chemotherapy and

Standard Radiation vs.

Accelerated

Concomitant Boost

Radiation

IMRT for

Oropharyngeal Cancer



Concurrent Accelerated

Radiation and Cisplatin

(P) vs. Concurrent

Accelerated Radiation

with Cisplatin and

Cetuximab (P-X)



9501

[4,

5]



0129

[6]



0522

[8]



0022

[7]



NR



Induction phase

only: NCI CTC v

1.0, All else:

RTOG/EORTC

criteria



Induction

Chemotherapy and

Radiation vs.

Concurrent

Chemoradiation vs.

Radiation for Advanced

Stage Laryngeal Cancer



9111

[2,

3]



NR



NR



Scale

RTOG/EORTC

criteria



Description

Hyperfractionation vs.

Conventional

Fractionation in T2

Laryngeal Cancer



#

9512

[1]



Acute

1

QD:

45/119

(38 %),

BID:

44/120

(37 %)

NR



NR



21 %



NR



NR



2

QD:

56/119

(47 %),

BID:

55/120

(46 %)

NR



4

0



0



Outside RT portal: P: 1 %,

P-X: 20 %

Inside RT portal: P: 15 %,

P-X: 25 %



10 %



Induction:

Induction:

16/156

0/156

(10 %),

(0 %), CRT:

CRT:

2/171

10/171

(1 %), RT:

(6 %), RT:

0/171 (0 %)

15/171

(9 %)

RT: 20/209 RT: 1/209

(10 %),

(<1 %),

combined:

CRT: 0

14/204

(7 %)

Standard: 31/361 (9 %),

CCB: 35/360 (10 %)



3

QD: 6/119

(5 %), BID

13/120

(11 %)



0



0



NR



0



0



5

0



NR



NR



NR



Induction:

51/154

(33 %),

CRT:

58/157

(37 %), RT:

59/158

(37 %)

NR



Late

1

QD: 41/118

(35 %),

BID:

41/119

(34 %)



Table 5.1 Acute and late skin toxicity as assessed in RTOG radiation therapy-based clinical trials in head and neck cancer



NR



5%



NR



Induction:

16/154

(10 %),

CRT:

16/157

(10 %), RT:

20/158

(13 %)

NR



2

QD: 5/118

(4 %), BID:

14/119

(12 %)



RT: 0/208

(0 %), CRT:

3/201 (1 %)



Induction:

1/154

(1 %), CRT:

0/157

(0 %), RT:

1/158 (1 %)



4

0



0



0



0



NR



0



0



5

0



Head and Neck Cancer

(continued)



Outside RT portal: P: 2 %,

P-X: 4 %

Inside RT portal: P: <1 %,

P-X: <1%P-X:



0



Standard: 5/351 (1 %),

CCB: 2/343 (<1 %)



RT: 2/208

(1 %), CRT:

2/201 (1 %)



Induction:

5/154

(3 %), CRT:

1/157

(1 %), RT:

2/158 (1 %)



3

QD: 0/118

(0 %), BID:

1/119 (1 %)



5

51



Description

IMRT with Concurrent

and Adjuvant

Chemotherapy for

Nasopharyngeal Cancer

Radiation with

Concurrent and

Adjuvant Chemotherapy

and Bevacizumab for

Nasopharyngeal Cancer



Scale

Systemic and

acute: NCI CTC v

2.0, Late: RTOG

criteria

NCI CTCAE v 3



2

30/68

(44 %)



18/44

(41 %)



Acute

1

16/68

(24 %)



12/44

(27 %)



9/44 (20 %)



3

9/68 (13 %)



0



4

0



0



5

0



16/41

(39 %)



Late

1

16/64

(25 %)



5/41 (12 %)



2

3/64 (5 %)



0



3

0



0



4

0



0



5

0



RTOG radiation therapy oncology group, vs. versus, EORTC European Organization for Research and Treatment of Cancer, QD daily, BID twice daily, v version, NR not reported,

CRT concurrent chemoradiation, RT radiation therapy, IMRT intensity modulated radiation therapy



0615

[10]



#

0225

[9]



Table 5.1 (continued)



52

S.S. Yom et al.



5



Head and Neck Cancer



5.2



Management of Skin

Reaction



Radiation-induced skin reaction in the head and

neck region can usually be visibly detected within

the first few weeks of treatment as a mild erythema, to be followed by a period of hyperpigmentation (“tanning”) and dry desquamation or

peeling. In the fifth to seventh week of treatment,

this reaction can progress rapidly to moist desquamation. In some cases, if the reaction is not controlled aggressively by means of supportive care

or adjustment of the radiation plan, the result can

be a large-scale deep desquamation and even

necrosis of the underlying soft tissues. When a

skin reaction begins, it will typically accumulate

in severity, so the areas that begin to manifest reaction earliest in the treatment course will be those

that are most severely affected in the last third of

the treatment course. The peak reaction will occur

at the time of the maximum dose delivery to that

area of tissue and will continue for another few

weeks. The time to resolution is variable but can

be prolonged, over the course of several weeks in

the case of the most severe reactions.

Historically, skin reactions were quite severe

as a routine in HNC, but with the advent of more

sophisticated planning techniques and improvements in preventive and supportive care, the level

of suffering during HNC radiation can now be

managed more effectively. While most practitioners will start a preventive program to try to

delay the onset of severe skin reactions, no highquality data has established the efficacy of these

interventions. There is very likely some degree of

individual variation in patients’ responses to radiation therapy; in the future, genomic approaches

may yield measures of sensitivity to predict

patients’ skin reactions [24]. In the clinical setting, it is key to recognize an unusual degree of

sensitivity in a particular individual early in the

treatment course, and if the reaction is highly out

of proportion to past experience with similar

patients, to consider an adjustment accordingly.

Once a skin reaction has begun, the immediate

goal should be to delay its progression to a higher

level. An important component of management is

the proper identification of the reaction’s severity.



53



In practice, most radiation oncologists are generally familiar with the RTOG grading scale, which

labels the level of skin reaction as: grade 1, erythema or dry desquamation; grade 2, tender or

bright erythema or patchy moist desquamation;

grade 3, confluent moist desquamation outside of

skin folds; grade 4, ulceration or hemorrhagic

necrosis; grade 5, death related to treatment effects.

Table 5.2 presents the evolution of skin reactions

as recorded in some case series as well as selected

examples of special cases of skin toxicity.

Clinical practice guidelines on the management of skin toxicity remain quite limited. For

example, the MASCC Skin Toxicity Study Group

conducted an extensive literature review on the

management of acute and late radiation-related

skin reactions. It is important to note that the

majority of these recommendations were based

on studies from the breast cancer literature. The

recommendations included washing with water

with or without a mild soap, allowing the use of

antiperspirants, and topical prophylactic corticosteroids such as mometasone to reduce discomfort and itching. The group found some evidence

supporting the use of silver sulfadiazine cream

and insufficient evidence to support the use of

trolamine, topical sulcrate, hyaluronic acid,

ascorbic acid, silver leaf dressing, light-emitting

diode lasers, Theta cream, dexpanthenol, calendula, proteolytic enzymes, sucralfate, oral zinc,

and pentoxifylline. For telangiectasia, the panel

recommended pulse dye laser for improvement

of visual appearance and the use of pentoxifylline and vitamin E for fibrosis [25]. These are

more limited recommendations than can be

found in the nursing and wound care literature.



5.3



Impact of Technical Choices

on the Skin



The widespread adoption of intensity modulated

radiation therapy (IMRT) for HNC irradiation

has resulted in characteristic patterns of effects

on the skin surface. Conventional threedimensional (3D) treatments with large collimated fields resulted in a more uniform level of

dose delivery to large swathes of skin; these



S.S. Yom et al.



54



effects could not be easily manipulated in the

planning process. With IMRT, areas of skin may

be deliberately spared during the planning process (by drawing the external skin as a structure

to avoid), but superficial external areas which are

not spared, or which are deliberately targeted,

are at a very high risk of reaction. The doses to

the skin, particularly around the lateral aspects of

the lower neck, in a “collar” region, can be much

higher with IMRT because of the multiple beam

angles typically used in step and shoot or

rotational plan designs, which tangentially

glance off the surface of the skin (Table 5.3) [26].

Furthermore, unanticipated “beam path” effects,

such as alopecia to the occipital scalp, have been

documented occurring at the exit points of the

IMRT beams [27].

Some special technical notes apply to

IMRT. When scars are targeted for high dosage,

such as in cases of extracapsular extension, there

will be an accordant skin reaction in that area

and anticipatory management should be part of

the plan (Table 5.3). Or, in some cases, IMRT

plans may be matched to abutting conventional

fields, such as the commonly used technique of

the anteroposterior conventional field used to

treat the low neck. In these cases, special care

must be taken not to allow the skin to be “hot” at

the junction. Of course, this same caveat also

should be strongly applied to any abutting conventional photon fields and particularly to the

rarely used situation of abutting electron fields.

In these situations, thermoluminescent dosimeter measurements are highly encouraged to confirm the dose delivered in the junctional areas, as

most treatment planning systems cannot model

the skin dose as accurately as they model the

deep tissue doses.



5.4



Patient-Related Factors

Affecting Acute Skin Toxicity



5.4.1



Age



that older patients are less likely to receive concurrent chemotherapy or more aggressive forms

of radiation therapy.



5.4.2



A poor nutritional status will prevent repair of tissue damage. This is a common and serious risk

for head and neck cancer patients, as undernourished patients are at high risk for skin damage

and prolonged wound healing [29].



5.4.3



Ethnicity



The “redhead” phenotype, which is associated

with polymorphisms in the melanocortin-1 receptor gene, has been found to produce unexpectedly

severe acute reactions to radiation therapy [30].

Furthermore, dark-skinned persons will frequently show earlier and more severe desquamation and late onset of hypopigmentation in

severely damaged areas [31].



5.4.4



Rheumatologic Disorders



Patients who have diagnoses of lupus, rheumatoid

arthritis, dermatomyositis, or other collagenvascular disorders may tolerate the treatment

course relatively well but suffer from greater late

toxicity. The radiation therapy can result in prolonged healing and greater degree of fibrosis [32].



5.4.5



Medical Conditions



Poor circulation affects the ability of the cutaneous tissue to heal. These factors include diabetes,

hypertension, vascular compromise, renal insufficiency, and smoking [33–35].



5.4.6

In a study of breast cancer patients, younger age

was found to be a predisposing factor to greater

skin toxicity [28]. A confounding factor may be



Nutrition



Obesity



Obese patients will be at higher risk for medical

comorbidities that limit healing potential but also



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