typically occur several days to weeks after commencement of RT and after multifraction-
ated doses totaling 20 Gy Archambeau et al. 1995
; Chopra and Bogart 2009
; Salvo et al. 2010
; Feight et al.
2011 . Dose tolerance in normal skin
is 45 Gy with increasing symptoms with greater cumulative RT doses and concomitant chemo-
therapy Archambeau et al. 1995
. Fluorouracil and epidermal growth factor receptor inhibitors
such as cetuximab have been reported to worsen radiation dermatitis in adult patients Archambeau
et al. 1995
; Budach et al. 2007
. Concurrent che- motherapy with radiosensitizers such as dactino-
mycin and doxorubicin may play a role in the severity of radiation dermatitis in pediatric
patients but has not been characterized in part due to the scheduling of these agents around RT
Archambeau et al.
1995 ; Krasin et al.
2009 .
Areas most affected are those containing skin folds such as the axillae, groin and inframam-
mary folds Feight et al. 2011
. The earliest skin changes are pruritus, mild erythema, anhydrosis,
and dry desquamation progressing to tender ery- thema, edema, and moist desquamation and, in
severe cases, ulceration and necrosis. Data on incidence of dermatitis in children are lacking.
Radiation recall, which can be precipitated by multiple agents and can occur days to years after
RT, most often presents as low-grade dermatitis in a previously irradiated region although more
severe reactions can also occur Burris and Hurtig
2010 .
Although there are a large number of adult studies which have reported on prevention and
management of acute radiation dermatitis, many have small patient numbers with confl icting
results. Pediatric data are almost completely lacking with only one reported study with 45
patients Merchant et al.
2007 . Multiple system-
atic reviews have been conducted though which are a useful guide from which to give direction
Bolderston et al. 2006
; Kedge 2009
; Kumar et al.
2010 ; Salvo et al.
2010 ; Feight et al.
2011 ;
McQuestion 2011
; Chan et al. 2012
; Wong et al. 2013
. General management recommendations include the use of loose fi tting clothing, preven-
tion of scratching or other abrasive activities, protection from the sun with hats and sunscreen,
avoidance of temperature extremes, avoidance of cornstarch or baby powder especially to skin
folds, use of an electric razor rather than a straight blade, use of non-aluminum-based deodorant on
intact skin, avoidance of cosmetic products in the treatment fi eld, avoidance of swimming in lakes
or chlorinated pools, and use of gentle, non- perfumed soaps and lotions Feight et al.
2011 ;
McQuestion 2011
. Although initially thought that washing of skin and hair in the radiation fi eld
would lead to increased toxicity, multiple studies have shown this to be safe Bolderston et al.
2006 ; Kumar et al.
2010 ; Salvo et al.
2010 ; Feight
et al. 2011
; McQuestion 2011
; Chan et al. 2012
; Wong et al.
2013 . It is vital though that the
irradiated areas be dry at the immediate time of treatment to prevent increasing the RT dose to the
skin surface Bernier et al. 2008
. Multiple topical agents for the prevention and
treatment of radiation dermatitis have been studied including aloe vera, steroid creams, trola-
mine Biafi ne
®
, calendula marigold extract, hyaluronic acid Xclair
®
, sucralfate, silver sulfa- diazine, 3M™ Cavilon™ no-sting barrier fi lm,
and petroleum-based ointment Aquaphor, among other more obscure substances Salvo
et al. 2010
; Feight et al. 2011
; McQuestion 2011
; Wong et al.
2013 . Certain agents such as aloe
vera, sucralfate, and trolamine are clearly without benefi t, while others such as calendula, Aquaphor,
hyaluronic acid, steroid creams, and silver sulfa- diazine are lacking in evidence Kumar et al.
2010 ; Salvo et al.
2010 ; Feight et al.
2011 ; Wong
et al. 2013
. Benefi t of silymarin milk thistle extract has also been reported in a nonrandom-
ized trial Becker-Schiebe et al. 2011
. Due to the lack of consistent and well-powered results, rec-
ommendations from the systematic reviews are variable with Salvo et al.
2010 and Chan et al.
2012 favoring no topical agent, McQuestion
2011 and Feight et al.
2011 endorsing calen-
dula and hyaluronic acid, Bolderston et al. 2006
supporting topical steroids, Kumar et al. 2010
favoring calendula, Cavilon™, and topical ste- roids, and Wong et al.
2013 sanctioning topical
steroids and silver sulfadiazine. All agree that larger, prospective, better designed studies are
required to answer the many remaining questions
about effi cacy. Finally, the majority of studies address prevention of symptoms, and thus there
is even less evidence to support topical therapy as treatment for radiation dermatitis Salvo et al.
2010 ; Wong et al.
2013 .
Prophylactic oral agents including zinc, proteolytic enzymes Wobe-Mugos E, pentoxi-
fylline, and sucralfate and dressings for manage- ment of moist desquamation such as hydrogels
and hydrocolloids e.g., DuoDERM
®
, Spenco 2nd Skin
®
, Intrasite™, silver leaf, moisture vapor permeable Tegaderm™, soft silicone
Mepilex
®
, GM-CSF impregnated, gentian vio- let, and more obscure dressings are also discussed
in the systematic reviews Kedge 2009
; Kumar et al.
2010 ; Salvo et al.
2010 ; Feight et al.
2011 ;
McQuestion 2011
; Wong et al. 2013
. As with the topical agents, poor study design and lack of
power limit conclusions that can be made on any of these agents Kedge
2009 ; Kumar et al.
2010 ;
Salvo et al. 2010
; Feight et al. 2011
; McQuestion 2011
; Wong et al. 2013
. Kedge 2009
notes in her review of hydrogels and hydrocolloid dress-
ings that although improved healing may not occur with these agents, patient comfort may be
an important benefi t in some cases.
13.5 Head and Neck
Complications
Radiotherapy to the head and neck can lead to complications in multiple different structures
including the oral mucosa, salivary glands, bone, masticatory musculature, dentition, middle and
outer ear, larynx, pharynx, and upper esophagus. The most common side effects with RT to the
oral mucosa and salivary glands include mucosi- tis, taste loss, parotitissialadenitis, xerostomia,
trismus, and osteoradionecrosis Kielbassa et al.
2006 . Mucositis and taste loss are transitory,
while xerostomia can be a long-term complica- tion although conformal radiation therapy and
proper planning have been shown to reduce this risk Kielbassa et al.
2006 ; Jensen et al.
2010a .
Head and neck cancer patients receiving RT must also be monitored for oropharyngeal candidiasis
Bensadoun et al. 2011
. Serous otitis media and externa, laryngeal edema, dysphagia, and pha-
ryngeal dysfunction can all occur. Tooth decay, sensorineural hearing loss, osteonecrosis, and
bone growth arrest are long-term effects that must be considered but are beyond the scope of
this chapter.
13.5.1 Oral Mucositis
Mucositis is a common and debilitating compli- cation of chemoradiation occurring several days
to weeks after RT initiation which can lead to treatment interruption, dose-limiting toxicity,
and decreased patient quality of life and is most likely to occur in patients receiving high-dose
radiation for head and neck cancers e.g., 60–70 Gy, with 85 of adult patients clinically
affected Sonis et al.
2004 ; Peterson et al.
2011 .
Incidence is dependent on the underlying thera- peutic regimen with combination chemoradiation
to the head and neck being a more likely culprit as well as total body irradiation TBI with HSCT
Sonis et al.
2004 ; Peterson et al.
2011 . Incidence
in children has not been widely reported but is likely similar to that for adults Allen et al.
2010 ;
Qutob et al. 2013b
. Multiple scoring systems have been utilized in the literature, and only some
have been validated for children Sonis et al. 2004
; Sung et al. 2007b
; Tomlinson et al. 2007
. Due to the large number of adult trials report-
ing on management of oral mucositis, multiple clinical practice guidelines and systematic
reviews from ASCO, ESMO, MASCC International Society of Oral Oncology ISOO,
and the Cochrane Collaboration are available in the literature to help guide management Keefe
et al.
2007 ; Hensley et al.
2009 ; Clarkson et al.
2010 ; Peterson et al.
2011 ; Worthington et al.
2011 ; Gibson et al.
2013 . Pediatric data are lim-
ited to small studies with variable treatment designs and therefore extrapolation from adult
studies is required Allen et al. 2010
; Qutob et al. 2013b
. Treatment of radiation-induced oral mucositis is similar to chemotherapy-induced
mucositis; the interested reader should refer to Chap.
11 for a more detailed review of mucositis
treatment guidelines.
Prior to the initiation of chemoradiation, the pediatric patient should have an oral exam to
determine what, if any, treatments are required to help prevent the development of mucositis and to
ensure there is no interference with the radiation fi eld Otmani
2007 ; Barbería et al.
2008 ; Qutob
et al. 2013a
. If possible, cavities should be fi lled and fi xed appliances in the radiation fi eld
removed 7–10 days before the initiation of ther- apy Barbería et al.
2008 . Families and patients
should be advised in regard to the importance of maintaining oral hygiene including regular tooth
and tongue brushing with a soft brush and fl uori- dated toothpaste in children ≥18 months and
regular mouth washing Qutob et al.
2013 b
. A standardized multidisciplinary hospital oral
care protocol has been shown benefi cial, as well as bland rinses such as saline or sodium bicar-
bonate; chlorhexidine has not been proven help- ful Keefe et al.
2007 ; Peterson et al.
2011 ;
McGuire et al. 2013
. Nutritional status should be monitored and those at risk for malnutrition
5 weight loss from baseline should be started on total parenteral nutrition TPN if with
orogastrointestinal mucositis or have percutane- ous endoscopic gastrostomy PEG placement if
with a head and neck tumor Ladas et al.
2005 .
Additionally, hydration status in patients with severe mucositis must be monitored with intrave-
nous fl uids given if required. Multiple well-studied agents in adult patients
receiving RT have not been shown benefi cial including cryotherapy i.e., ice chips, oral cool-
ing, antimicrobial lozenges, misoprostol mouth- wash, amifostine, glutamine, and pilocarpine for
the prevention of oral mucositis and oral sucral- fate for treatment of mucositis Keefe et al.
2007 ;
Hensley et al. 2009
; Gibson et al. 2013
; Jensen et al.
2013 ; Nicolatou-Galitis et al.
2013 ; Peterson
et al. 2013
; Saunders et al. 2013
; Yarom et al. 2013
. Therapies that have shown potential ben- efi t include prophylactic zinc, morphine mouth
rinse, doxepin rinse, morphine patient-controlled analgesia PCA, use of midline radiation blocks
with EBRT, not utilized with IMRT, benzyda- mine locally acting nonsteroidal anti-
infl ammatory, low-level laser therapy LLLT, and palifermin keratinocyte growth factor-1
[KGF-1] Keefe et al. 2007
; Hensley et al. 2009
; Clarkson et al.
2010 ; Peterson et al.
2011 ; Gibson
et al. 2013
; Migliorati et al. 2013
; Nicolatou- Galitis et al.
2013a ; Raber-Durlacher et al.
2013 ;
Saunders et al. 2013
; Yarom et al. 2013
. The strongest evidence in the adult literature exists
for benzydamine, LLLT and palifermin. Of note, benzydamine has not been approved by the
United States Food and Drug Administration.
LLLT is recommended in adult patients receiv- ing HSCT with or without TBI and head and neck
patients undergoing RT Peterson et al. 2011
; Migliorati et al.
2013 . A pilot study of LLLT in
children showed potential benefi t in the preven- tion of chemotherapy-induced mucositis
Abramoff et al. 2008
. Palifermin, 60 mcgkg day, for 3 days prior to conditioning and 3 days
posttransplantation for autologous and possibly allogeneic HSCT with TBI has shown benefi t in
adult patients Keefe et al. 2007
; Hensley et al. 2009
; Raber- Durlacher et al. 2013
. Recent stud- ies in adult head and neck cancer patients are
promising in reducing the severity and duration of mucositis symptoms although without improve-
ment in event-free and overall survival Le et al.
2011 ; Henke et al.
2011 . Data on palifermin
usage in the pediatric population are signifi cantly limited. Srinivasan et al.
2012 recently reported
on a phase I dose-fi nding study in 12 children receiving myeloablative HSCT and found that
90 mcgkgday was tolerated with skin rash being the most common side effect; mucositis was seen
in only 25 of the cohort but without a compara- tive control group. See Chap.
11 for a full discus-
sion regarding oral mucositis and mouth care.
13.5.2 Dysgeusia
Patients undergoing radiation for head and neck tumors are at risk for altered taste due to direct
radiation effect on the fungiform papillae and taste buds Otmani
2007 . Taste loss can precede
mucositis with histologic signs of degeneration and atrophy occurring after 10 Gy, with taste loss
increasing exponentially with higher cumulative RT doses, and with bitter and acid fl avors being
most affected Kielbassa et al.
2006 . Pediatric
