Radiation Dermatitis 

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Background Information

Description

  •  radiation dermatitis is a radiation-induced skin condition, with a range of symptoms from erythema or desquamation to fibrosis, that can lead to significant discomfort, reduced mobility, and decreased quality of life(1,2,3,4)
  •  severe radiation dermatitis may also limit utilization of further radiation therapy(1,2,3,4)
  •  radiation dermatitis is most commonly caused by external beam ionizing radiation therapy for malignancies, but may also be caused by other radiation exposures, such as radiation for interventional procedures, accidental environmental exposures, or occupational exposures(2,3)

Also Called

  •  radiodermatitis
  •  radiation injury
  •  radiation-induced skin reaction

Types

  • acute radiation dermatitis(1,2,3,4)
    •  early skin changes that manifest ≤ 90 days of radiation therapy initiation
    •  severity can range from erythema to dry or moist desquamation
  • chronic radiation dermatitis(1,2,3,4,5)
    •  skin reactions develop > 90 days after completion of radiation therapy
    •  usually permanent, progressive, and irreversible, causing significant impact on quality of life
    •  can manifest as fibrosis, telangiectasia, chronic ulcers, radiation-induced morphea, or radiation recall

Epidemiology

Who Is Most Affected

  •  some form of radiation dermatitis occurs in 95% of patients who receive external beam ionizing radiation therapy for cancer treatment(1,2,3,5)
  •  patients with breast cancer, head and neck cancer, lung cancer, and sarcoma are most commonly affected due to higher doses of radiation and proximity of target organ to skin(2,3)
  • prevalence with breast cancer
    • 81% of women treated with postoperative radiation therapy for breast cancer developed at least mild radiation dermatitis in a single center in China between June 2016 and July 2017
    • 97% of women undergoing radiation therapy post surgery for breast cancer experienced radiation dermatitis, with hyperpigmentation being the most common and uncomfortable symptom
      •  based on cross-sectional study
      •  111 women (mean age 50 years) who had breast-conserving surgery or radical mastectomy for breast cancer and were receiving the last 2 weeks of radiation therapy at a single center in South Korea were assessed
      • 97.3% of women had radiation dermatitis and on average experienced 8.6 skin toxicities including
        •  91% had hyperpigmentation
        •  88.3% had erythema
        •  87.4% had skin dryness
        •  84.7% had scleroderma
        •  83.8% had roughness
        •  88.3% experienced pain
        •  86.5% had itching
        •  86.5% had irritation
        •  81.1% experienced burning sensation
      • 50.9% went to hospital for treatment of radiation dermatitis
        •  90.7% consulted radiation oncologist
        •  5.6% went to a breast surgeon
        •  3.7% presented to dermatologist
        •  1.9% presented to oriental medicine doctor
      •  79.8% of women sought information regarding radiation-induced skin reactions and 59.4% used various topical products like humectants, aloe cream, prescribed ointments, or easydew cream
      •  Reference – Qual Life Res 2017 Jul;26(7):1713
  •  prevalence of moderate-to-severe radiation dermatitis in 32.5% of 2,152 patients receiving radiation therapy in combination with cetuximab for head and neck squamous cell carcinoma (Crit Rev Oncol Hematol 2017 Dec;120:98)
  •  patients receiving radiation with fluoroscopy, such as coronary angiography, embolization procedures, and indwelling catheter placements may also be at risk for radiation dermatitis, particularly if the external beam ionizing radiation is > 2 Gy (Cardiovasc Intervent Radiol 2017 Aug;40(8):1131full-text)

Risk Factors

  • treatment-related (also called extrinsic) factors affect risk of radiation dermatitis for patients having radiation therapy(1,2,3,5)
    • type of radiation, dosage, and number of fractions
      •  higher total radiation dose associated with greater risk of radiation dermatitis
      •  dose fractionation schedule (conventional fractionation associated with higher risk than hypofractionated)
      •  type of external beam used (field-in-field three-dimensional [3-D] techniques or intensity-modulated radiation therapy [MRT]) associated with reduced skin related toxicities (Breast Cancer (Dove Med Press) 2017;9:313full-text)
    • concurrent chemotherapy
      •  radiosensitizers, such as taxanes (docetaxel, paclitaxel), anthracyclines (doxorubicin), antimetabolites (gemcitabine, capecitabine), cetuximab
      •  vemurafenib, a BRAF inhibitor, and tamoxifen have also been implicated
    •  site of treatment
    •  volume and surface area of irradiated tissue
  • patient-related (also called intrinsic) risk factors may also affect risk of radiation dermatitis for patients having radiation therapy(1,2,3,5)
    •  older age
    •  female gender
    •  smoking
    •  poor nutritional status
    •  high body mass index (BMI)
    •  presence of skin folds in treatment area
    •  large breast cup size or patients with implants and breast reconstruction for patients receiving radiation therapy for breast cancer
    •  skin disorders such as acne, psoriasis, or atopic eczema increase risk of chronic radiation dermatitis
    •  coexisting disease, such as diabetes mellitus, connective tissue disorders (such as systemic lupus erythematosus, systemic sclerosis, and rheumatoid arthritis), or HIV infection
    •  genetic factors that may affect DNA repair mechanisms, such as xeroderma pigmentosum, ataxia telangiectasia, Gorlin syndrome, Gardner syndrome, hereditary malignant melanoma, and dysplastic nevus syndrome
    •  ultraviolet (UV) exposure
  • risks for acute radiation dermatitis
    • conventional fractionation regimens, regional nodal irradiation, advanced disease stage, and higher BMI associated with higher risk of acute radiation dermatitis in women with breast cancer
      •  based on 1 prospective cohort study and 1 retrospective cohort study
      • 280 women (median age 60 years) who had breast cancer and were treated with up-front surgery followed by radiation therapy with or without adjuvant chemotherapy from 2008 to 2015 were assessed
        •  50 women had postmastectomy radiation therapy (PMRT) and 230 had postlumpectomy radiation therapy (intact breast) of which 56 had hypofractionation and 174 had conventional fractionation
        •  adjuvant chemotherapy in 31%
        •  comorbidities (≥ 1 of diabetes mellitus, hypertension, or coronary artery disease) in 47%
        •  overall, moist desquamation in 11.4% and grade ≥ 2 radiation dermatitis in 31.5%
        • comparing PMRT vs. postlumpectomy radiation therapy
          •  given regional nodal irradiation 84% vs. 10% (p = 0.001)
          •  treated with chemotherapy 74% vs. 21.7% (p = 0.007)
          •  development of moist desquamation in 24% vs. 8.7% (p = 0.005)
          •  grade ≥ 2 radiation dermatitis in 48% vs. 27.8% (p = 0.007)
        • comparing conventional vs. hypofractionation radiation therapy in patients with postlumpectomy radiation therapy
          •  regional nodal irradiation in 18.4% vs. 0% (p = 0.001)
          •  treated with chemotherapy 25.9% vs. 8.9% (p = 0.007)
          •  moist desquamation in 10.9% vs. 1.8% (p = 0.05)
          •  grade ≥ 2 radiation dermatitis in 30.4% vs. 7.1% (p < 0.001)
        • development of moist desquamation associated with
          •  adjuvant chemotherapy (odds ratio [OR] 3.74, p = 0.04)
          •  use of regional nodal irradiation (OR 3.29, p = 0.03)
          •  BMI ≥ 30 (OR 3.29, p = 0.03)
        •  Reference – Adv Radiat Oncol 2018 Jan;3(1):8full-text
      • 392 women (mean age 56 years) with stage 0-III breast cancer who underwent breast-conserving surgery and were indicated for radiation therapy with or without nodal radiation between December 2008 and July 2014 at single center in Miami, Florida were assessed
        •  overall, grade 0-1 dermatitis in 48%, grade 2 dermatitis in 49.8%, and grade 3 dermatitis in 2.2%
        • development of grade 2-3 radiation dermatitis associated with
          •  higher BMI (odds ratio [OR] 2.09, 95% CI 1.15-3.82)
          •  advanced disease stage (OR 1.82, 95% CI 1.06-3.11)
          •  estrogen-positive/progesterone negative status (OR 2.74, 95% CI 1.26-5.98)
          •  conventionally fractionated regimens (vs. hypofractionated) (OR 3.25, 95% CI 1.76-6.01)
        •  Reference – Cancer Med 2016 Mar;5(3):454full-text
    • skin to tumor distance < 11 mm, maximum skin total dose ≥ 52 Gy relative biological effectiveness (RBE) or surface area irradiated with 40 Gy (RBE) ≥ 25 cm2 may predict more severe acute radiation dermatitis in adults treated with carbon ion radiation therapy (CIRT) for locally advanced malignant bone and soft tissue tumors
      •  based on prospective cohort study
      •  22 adults (median age 61 years, 73% males) who were treated with CIRT for locally advanced malignant bone and soft tissue tumors were assessed and followed for a median of 42.5 months
      •  acute grade 1 radiation dermatitis in 71% and acute grade 2 radiation dermatitis in 29%
      •  chronic grade 1 radiation dermatitis in 71%
      • comparing adults with acute grade 1 reactions vs. adults with acute grade 2 reactions
        •  median skin to tumor distance (STD) of 23 mm vs. 5 mm (p = 0.007)
        •  median maximum skin total dose (Dmax) of 39 Gy (RBE) vs. 62 Gy (RBE) (p < 0.001)
        •  median area irradiated with 40 Gy (RBE) of 0 cm2 vs. 57 cm2 (p = 0.002)
      • for predicting development of acute grade 2 radiation dermatitis
        •  STD at a cutoff value of 11 mm had sensitivity of 86% and specificity 87%
        •  Dmax at cutoff value of 52 Gy (RBE) had sensitivity 100% and specificity 93%
        •  surface area irradiated with 40 Gy (RBE) at cutoff value of 25 cm2 had sensitivity 100% and specificity 80%
      •  Reference – Radiat Oncol 2017 Nov 22;12(1):185full-text
  • risk factors for chronic radiation dermatitis
    • compared to radiation therapy alone, concurrent chemotherapy with radiation therapy associated with higher risk of developing grade ≥ 3 acute dermatitis and grade ≥ 2 late toxicities in adults with soft tissue sarcoma
      •  based on retrospective cohort study
      • 80 adults (median age at diagnosis 53 years) with soft tissue sarcoma treated with conservative surgery followed by radiation therapy or concurrent chemotherapy plus radiation therapy (CCRT) between 1990 and 2012 at a single center in France were assessed for a median follow up of 68 months
        •  51 adults received only radiation therapy and 29 received CCRT
        •  25 adults on CCRT received doxorubicin monotherapy, 3 received combination of doxorubicin, ifosfamide, dacarbazine, and mesna, 1 received epirubicin and dacarbazine
      •  no significant differences between CCRT and radiation only for disease-free survival, distant failure-free survival, or overall survival
      •  CCRT associated with significantly higher frequencies of grade 3 sarcomas, deep localization, and unfavorable histological types
      •  CCRT associated with higher risk of grade ≥ 3 acute dermatitis (odds ratio [OR] 6.99, 95% CI 2.28-21.47)
      •  8 adults (10%) developed late toxicity of grade ≥ 2 affecting several tissues, including telangiectasia, fibrosis, lymphedema, neuropathy, fracture, and functional impairment
      •  CCRT associated with higher risk of grade ≥ 2 late toxicity (OR 4.17, 95% CI 0.96-18.19) (not significant)
      •  Reference – Radiother Oncol 2017 Oct;125(1):160
    • concurrent chemotherapy and radiation therapy associated with higher risk of late development of grade 2/3 fibrosis and breast retraction than sequential radiation therapy followed by chemotherapy in women with breast cancer
      •  based on follow-up of randomized trial
      • 206 women (mean age 47 years) with pT1 or pT2 breast cancer and negative surgical margins post breast-conserving surgery were randomized to sequential chemotherapy treatment followed by radiation therapy vs. concurrent chemotherapy and radiation therapy between 1997 and 2002 at single center in Italy
        •  chemotherapy consisted of cyclophosphamide, 5-fluorouracil, and methotrexate
        •  whole breast radiation was delivered by tangential field at daily dose of 2.5 Gy/fraction, 5 times weekly, to total dose of 50 Gy
      •  102 women available for assessment for late toxicities after a median follow-up of 15 years
      • comparing sequential vs. concurrent radiation therapy
        •  grade 2/3 fibrosis in 18.4% vs. 41.5% (p = 0.013)
        •  grade 2/3 breast retraction in 14.3% vs. 39.6% (p = 0.006)
      • development of grade 2/3 fibrosis associated with
        •  concurrent chemotherapy and radiation therapy (odds ratio [OR] 3.75, 95% CI 1.19-11.79)
        •  tumor location in inferior half (OR 6.8, 95% CI 1.73-26.71)
        •  age (OR 1.09, 95% CI 1.02-1.17)
        •  boost energy (OR 2.57, 95% CI 1.33-4.96)
      • development of grade 2/3 breast retraction associated with
        •  concurrent chemotherapy and radiation therapy (OR 3.87, 95% CI 1.42-10.56)
        •  tumor location in inferior half (OR 4.42, 95% CI 1.37-14.24)
      •  Reference – Int J Radiat Oncol Biol Phys 2016 Jul 15;95(4):1201

Pathogenesis

  • exposure to radiation, including therapeutic medical use, accidental exposure, and occupational exposures can lead to radiation dermatitis(1,2,3,4)
    •  most commonly radiation dermatitis seen after radiation therapy for cancer treatment
    •  dermal reactions after radiology procedures with dosing > 2 Gy (200 rad), such as with fluoroscopically guided procedures, can occur but severe dermal injury is rare (Cardiovasc Intervent Radiol 2017 Aug;40(8):1131full-text)
  •  radiation dermatitis is caused by a combination of direct radiation injury and inflammatory response to the injury(1,2,3)
  • acute effects(1,2,3)
    • exposure to initial doses of radiation results in
      •  production of reactive oxygen species and free radicals that damage rapidly dividing cells of basal layer and underlying dermis
      •  DNA damage and alterations to the protein, lipid, and carbohydrate components of skin tissue
      •  generation of an inflammatory response caused by proinflammatory cytokine cascade, chemokines, receptor tyrosine kinase, and adhesion molecules
    •  every subsequent exposure to radiation results in a greater inflammatory response
    •  capillary dilation and increase in vascular permeability is hypothesized to cause transient erythema, the first cutaneous manifestation after initiation of treatment
    •  sustained generalized erythema (2-4 weeks after initiation) is characterized by epidermal degeneration and dermal edema due to the infiltration of leukocytes in underlying tissue
    •  higher doses of radiation (> 20 Gy) result in dry desquamation (thickened, scaly skin) due to the slow shedding of old skin cells and increased rate of mitosis in basal keratinocyte layer
    •  higher doses (≥ 40 Gy) can result in exudate release, referred to as moist desquamation
  • late chronic effects(1,2,3,5)
    • dermal fibroblasts play a key role in development of chronic radiation dermatitis
      •  radiation results in an increase in thrombin-induced transforming growth factor (TGF)-beta activation
      •  TGF-beta then activates fibroblasts and fibroblast-derived mediators resulting in in fibrotic changes
      •  leukocyte infiltration and atypical fibroblasts lead to atrophy, contraction, and fibrosis
    •  long-lasting cellular dysfunction and stromal and vasculature changes that impair cutaneous integrity can persist long after radiation injury
    •  telangiectasia development is hypothesized to be caused by acutely damaged microvasculature and the production of platelet-derived growth factor (PDGF) and fibroblast growth factor by damaged cells
    •  late skin reactions can also include hyperpigmentation or hypopigmentation
    •  increased risk of subsequent nonmelanoma cancers, such as basal cell carcinomas, keratoacanthomas, squamous cell carcinomas
    •  postradiation angiosarcoma diagnosed > 5 years after radiation treatment in 10 patients with breast cancer in case series (J Cutan Pathol 2017 May;44(5):456)

General Evaluation

Clinical Presentation

Acute Radiation Dermatitis

  •  acute radiation dermatitis is defined as occurring within 90 days from exposure(1,2,3)
  • patients may present with severities ranging from mild erythema to moist desquamation and ulceration(1,2,3)
    •  assess size, depth, morphological aspects, and color of affected areas
    •  skin reactions are generally dose-dependent and occur within a predictable time course

Table

Table 1: Typical Acute Skin Reactions by Radiation Dose and Time Since Exposure

Radiation DoseTime Post Initial ExposureAcute Skin Reaction
2 GyHoursTransient erythema
6-10 Gy7-10 daysFaint erythema and epilation
12-20 Gy2-3 weeksDefined erythema and hyperpigmentation
20-25 Gy3-4 weeksDry desquamation
30-40 Gy≥ 4 weeksMoist desquamation
> 40 Gy≥ 6 weeksUlceration
initial manifestation is transient erythema which occurs in ≤ 24 hours of exposure and often subsides within a few days(1,2,3)
 during weeks 2-4, patient can present with sustained erythema and additional skin changes including, dryness, hair loss, and hyperpigmentation(1,2,3)
 during weeks 3-6, pruritus, scaling, peeling, and flaking of dry skin, which are signs of dry desquamation typically are seen(1,2,3)
 in more severe cases, patients may present a few weeks from exposure with painful moist desquamation(1,2,3) skin appears moist, tender, and red with peeling skin, serous exudate and crusting
 edema, bullae, and exposure of dermis may occur
 moist desquamation associated with risk of infection
 consider withholding further radiation therapy till skin heals as there is higher risk of infection, sun damage, and ulcer formation
 patients may also present with radiation recall, an acute inflammatory skin reaction that occurs after chemotherapy in a region of the skin that was previously exposed to radiation(2,3) manifests with maculopapular eruptions, dry desquamation, pruritus, swelling, and ulcerations
 most commonly occurs if chemotherapy is administered ≤ 2 months after radiation therapy
 associated with anthracyclines, taxanes, and antimetabolites (such as, doxorubicin, gemcitabine, docetaxel), but also reported with epidermal growth factor receptor (EGFR) inhibitors, BRAF tyrosine kinase inhibitors
 ask about all of the following(1,2,3) type of oncological interventions
 type and dose of radiation therapy
 chemotherapy
 surgery
 previous skin complications
 comorbidities, such as diabetes, HIV, connective tissue disorders, genetic disorders (see also Risk factors)
 medication use
 previous surgery in the area, particularly breast reconstruction and implants
 some cancers associated with higher incidence of acute radiation dermatitis(3)

Table

Table 2: Radiation Dermatitis in Commonly Occurring Cancers

CTCAE/RTOG GradeGrade 0 (No Dermatitis)Grade 1 (Mild Dermatitis)Grade 2 (Moderate Dermatitis)Grade 3 and 4 (Severe Dermatitis)
Head and neck cancer1%20%57%23%
Breast cancer6%61%24%9%
Vulvar cancer0%11%67%22%
Anal cancer76%16%5%3%

Citation: Abbreviations: CTCAE, Common Terminology Criteria for Adverse Events; RTOG, Radiation Therapy Oncology Group.

Chronic Radiation Dermatitis

  • patients present with chronic radiation dermatitis several months to years after completion of radiation therapy(1,2,3,5)
    •  considered a true late-stage skin reaction that develops long after radiation therapy completion
    •  skin changes can be transient or may persist for years
  •  patients with chronic dermatitis may present to dermatologists or primary care clinicians, while patients with acute radiation dermatitis may be seen by radiation oncologists(2)
  • patients may present with any of following signs or symptoms(1,2,3,5)
    •  postinflammatory dyspigmentation of skin
    •  skin atrophy
    •  hyperkeratosis
    •  loss of skin appendages, hair follicles, sebaceous, and sudoriferous glands
    •  textural changes such as xerosis, scaling
    •  telangiectasia – dilation of small blood vessels
  • radiation-induced fibrosis is a severe, progressive, and irreversible complication, characterized by any of the following signs or symptoms(2,5)
    •  induration and retraction of the skin
    •  lymphedema
    •  joint motion restriction
    •  changes in skin appearance
    •  wounds
    •  ulcerations
  •  in some cases, patients can present with nonmelanotic cutaneous malignancies like basal cell carcinomas, keratoacanthomas, and squamous cell carcinomas(1)
  • radiation-induced morphea, a very rare complication includes pain and disfigurement of irradiated area(3)
    •  characterized by erythematous plaques and indurated papular lesions
    •  caused by abnormal fibroblast activity and deposition of thickened collagen
    •  can progress into radiation necrosis

Diagnosis

  • diagnosis of radiation dermatitis can be made clinically based on medical history of radiation exposure and clinical presentation of skin with typical findings(1,2,3,4)
    •  for acute dermatitis, skin findings range from erythema a few days or weeks after exposure to desquamation or ulceration of skin 3-4 weeks after exposure
    •  chronic dermatitis is diagnosed after at least 90 days from exposure with skin findings ranging from atrophy or telangiectasias to fibrosis
  •  consider scoring systems to grade severity and guide treatment(5)
  • consider noninvasive methods to measure various parameters(3)
    •  laser doppler perfusion imaging to measure changes in microcirculation
    •  quantitative ultrasound to measure skin thickness
    •  reflectance colorimetry, digital photography, and spectrophotometry to measure melanin and erythema indices of skin discoloration
  •  if secondary malignancy suspected with chronic radiation-induced fibrosis, consider biopsy and histopathological examination or magnetic resonance imaging (MRI) for evaluation(5)

Scoring Systems to Grade Severity

  •  no gold standard for measuring severity of radiation injury(3)
  • most widely used scoring systems include(3,4)
    •  National Institute of Health Common Toxicity Criteria-Adverse Event (CTCAE) version 4.0
    •  Radiation Therapy Oncology Group (RTOG)/European Organization for Research and Treatment of Cancer (EORTC) scale
    •  Late Effects Normal Tissue Task Force/ Subjective, Objective, Management, and Analytic (LENT/ SOMA) scale

Chronic Radiation Dermatitis

  • patients present with chronic radiation dermatitis several months to years after completion of radiation therapy(1,2,3,5)
    •  considered a true late-stage skin reaction that develops long after radiation therapy completion
    •  skin changes can be transient or may persist for years
  •  patients with chronic dermatitis may present to dermatologists or primary care clinicians, while patients with acute radiation dermatitis may be seen by radiation oncologists(2)
  • patients may present with any of following signs or symptoms(1,2,3,5)
    •  postinflammatory dyspigmentation of skin
    •  skin atrophy
    •  hyperkeratosis
    •  loss of skin appendages, hair follicles, sebaceous, and sudoriferous glands
    •  textural changes such as xerosis, scaling
    •  telangiectasia – dilation of small blood vessels
  • radiation-induced fibrosis is a severe, progressive, and irreversible complication, characterized by any of the following signs or symptoms(2,5)
    •  induration and retraction of the skin
    •  lymphedema
    •  joint motion restriction
    •  changes in skin appearance
    •  wounds
    •  ulcerations
  •  in some cases, patients can present with nonmelanotic cutaneous malignancies like basal cell carcinomas, keratoacanthomas, and squamous cell carcinomas(1)
  • radiation-induced morphea, a very rare complication includes pain and disfigurement of irradiated area(3)
    •  characterized by erythematous plaques and indurated papular lesions
    •  caused by abnormal fibroblast activity and deposition of thickened collagen
    •  can progress into radiation necrosis

Diagnosis

  • diagnosis of radiation dermatitis can be made clinically based on medical history of radiation exposure and clinical presentation of skin with typical findings(1,2,3,4)
    •  for acute dermatitis, skin findings range from erythema a few days or weeks after exposure to desquamation or ulceration of skin 3-4 weeks after exposure
    •  chronic dermatitis is diagnosed after at least 90 days from exposure with skin findings ranging from atrophy or telangiectasias to fibrosis
  •  consider scoring systems to grade severity and guide treatment(5)
  • consider noninvasive methods to measure various parameters(3)
    •  laser doppler perfusion imaging to measure changes in microcirculation
    •  quantitative ultrasound to measure skin thickness
    •  reflectance colorimetry, digital photography, and spectrophotometry to measure melanin and erythema indices of skin discoloration
  •  if secondary malignancy suspected with chronic radiation-induced fibrosis, consider biopsy and histopathological examination or magnetic resonance imaging (MRI) for evaluation(5)

Scoring Systems to Grade Severity

  •  no gold standard for measuring severity of radiation injury(3)
  • most widely used scoring systems include(3,4)
    •  National Institute of Health Common Toxicity Criteria-Adverse Event (CTCAE) version 4.0
    •  Radiation Therapy Oncology Group (RTOG)/European Organization for Research and Treatment of Cancer (EORTC) scale
    •  Late Effects Normal Tissue Task Force/ Subjective, Objective, Management, and Analytic (LENT/ SOMA) scale

Table

Table 3: Comparison of Commonly Used Radiation Skin Injury Scoring Systems

ScoreGrade 0Grade 1Grade 2Grade 3Grade 4Grade 5
CTCAE 4.0No change over baselineFaint erythema or dry desquamationModerate to brisk erythema, patchy moist desquamation of skin folds, moderate edemaConfluent moist desquamation other than skin folds and creases, bleeding with minimal trauma, pitting edemaSkin necrosis or full-thickness ulcerations, spontaneous bleedingDeath
RTOG/EORTCNo change over baselineFaint or dull erythema, epilation, dry desquamation, decreased sweatingTender or bright erythema, patchy moist desquamation, moderate edemaConfluent moist desquamation other than skin folds, pitting edemaUlceration, hemorrhage necrosisDeath
LENT/SOMANo change over baselineMinor symptoms that require no treatmentModerate symptoms that require conservative treatmentSevere symptoms with significant negative impact on daily activities, requires more aggressive treatmentIrreversible functional damage, needs therapeutic interventionDeath or organ loss

Citation: Abbreviations: CTCAE, Common Terminology Criteria for Adverse Events; EORTC, European Organization for Research and Treatment of Cancer; LENT, Late Effects Normal Tissue Task Force; RTOG, Radiation Therapy Oncology Group; SOMA, Subjective, Objective, Management, and Analytic.

Table

Table 4: Oncology Nursing Society (ONS)

ScoreObservation
0No change
1.0Faint or dull erythema
1.5Bright erythema
2.0Dry desquamation with or without erythema
2.5Small-to-moderate amount of moist desquamation
3.0Confluent moist desquamation
3.5Ulceration, hemorrhage, or necrosis
Douglas and Fowler (D&F)

Table 5: Douglas and Fowler (D&F)

ScoreObservation
0Normal
0.2550/50 doubtful if any difference from normal
0.5Very slight reddening
0.75Definite but slight reddening
1Severe reddening
1.25Severe reddening with white scale; “papery” appearance of skin
1.5Moist breakdown in 1 very small area with scaly or crusty appearance
1.75Moist desquamation in more than 1 small area
2Moist desquamation in 25% of irradiated area
2.25Moist desquamation in 33% of irradiated area
2.5Moist desquamation in 50% of irradiated area
2.75Moist desquamation in 66% of irradiated area
3Moist desquamation in most of irradiated area
3.25Moist desquamation in most of irradiated area with slight moist exudate
3.5Moist desquamation in most of irradiated area with moist exudates; necrosis
Radiation Dermatitis Severity (RDS) scales

Table 6: Radiation Dermatitis Severity (RDS)

ScoreObservation
0.0Normal or none
0.5Patchy faint/slight follicular erythema; faint hyperpigmentation
1.0Faint and diffuse erythema; diffuse hyperpigmentation; mild epilation
1.5Definite erythema; extreme darkening/hyperpigmentation
2.0Definite erythema/hyperpigmentation with fine dry desquamation; mild edema
2.5Definite erythema/hyperpigmentation with branny/scaly desquamation
3.0Deep red erythema with diffuse dry desquamation; peeling in sheets
3.5Violaceous erythema with early moist desquamation; peeling in sheets; patchy crusting
4.0Violaceous erythema with diffuse moist desquamation; patchy crusting; ulceration; necrosis
Reference – (3), J Invest Dermatol 2012 Mar;132(3 Pt 2):985full-text
 patient-reported scoring systems include Skindex-16 questionnaire
 Skin Toxicity Assessment Tool
 Radiation- Induced Skin Reaction Assessment Scale (RISRAS)
 6-point Likert scales
 EORTC breast cancer-specific quality of life questionnaire (QLQ-BR-23) – specific to breast-related symptoms
 Functional Assessment of Cancer Therapy-Breast (FACT-B) – specific to breast-related symptoms
 Reference – J Invest Dermatol 2012 Mar;132(3 Pt 2):985full-text, Breast Cancer (Dove Med Press) 2017;9:313full-text
Differential Diagnosis
contact dermatitis(3)
 radiation port dermatophytosis(3)
erythema multiforme(3)
Stevens-Johnson syndrome/toxic epidermal necrolysis(3)
 nephrogenic systemic fibrosis(5)
Management
Management Overview
 consider preventive measures to reduce incidence and severity of radiation dermatitis in patients undergoing radiation therapy for cancer treatment consider radiation therapy techniques that reduce skin related toxicities including field-in-field three-dimensional (3-D) techniques or intensity-modulated radiation therapy (IMRT), prone position during radiation (for breast treatment), and hypofractionation
 advise patients to practice daily hygiene including washing with water, with or without soaps or shampoos, and adopt good skin care practices, including sun protection with sun protective clothing and sun protection factor (SPF) ≥ 30
 use low-to-medium potency topical corticosteroid prophylactically 1-2 times daily prophylactic topical corticosteroids may reduce incidence of acute radiation dermatitis, specifically moist desquamation in women undergoing radiation therapy post modified radical mastectomy or breast-conservation surgery (level 2 [mid-level] evidence)
 options include mometasone furoate 0.1% cream
 hydrocortisone valerate 0.2% cream
 methylprednisolone 0.1% cream
 betamethasone 0.1% ointment
 beclomethasone spray 100 mcg/puff (2 puffs) twice daily
semi-permeable dressings (Mepilex Film, silver nylon dressings, 3M Cavilon No-sting Barrier) may be effective in preventing acute radiation dermatitis in patients receiving radiation therapy for cancer (level 2 [mid-level] evidence)
 limited evidence regarding use of nonsteroidal topical agentsprophylactic application of heparinoid moisturizer during radiation therapy and continued till 3 months post therapy may reduce development of desquamation in women with breast cancer (level 2 [mid-level] evidence)
 addition of silver sulfadiazine 1% cream to general skin care may reduce severity of radiation dermatitis in women with breast cancer undergoing radiation therapy after mastectomy and chemotherapy (level 2 [mid-level] evidence)
aloe vera may reduce acute radiation dermatitis in adults (level 2 [mid-level] evidence)
 limited evidence regarding use of systemic therapy or laser therapy to prevent radiation dermatitisprophylactic enteral glutamine may reduce radiation dermatitis in patients with breast cancer
pentoxifylline and vitamin E reported to prevent radiation-related capsular contraction of breast implants following mastectomy, immediate reconstruction, and adjuvant radiation therapy in women with breast cancer (level 3 [lacking direct] evidence)
photobiomodulation laser therapy applied immediately after each radiation therapy session may prevent development of ≥ grade 2 radiation dermatitis in women with breast cancer (level 2 [mid-level] evidence)
treatment for acute radiation dermatitis is generally supportive and depends on grade of reactionfor mild (grade 1) reactions, consider hydrophilic moisturizers and low-to-medium potency topical steroids
for moderate (grade 2 and 3) reactions, consider wound care measures to maintain moist wound environment and prevent secondary infection
for severe (grade 4) reactions, consider stopping radiation therapy till skin heals completely and a multidisciplinary approach of surgical debridement and reconstruction
treatment of chronic radiation dermatitis is multidisciplinary with wound care management, physical therapy, and pain management LPG mechanical massage after completion of radiation therapy associated with decrease in skin induration and increase in skin softness in women who had undergone breast conserving surgery followed by radiation therapy (level 2 [mid-level] evidence)
 inconsistent evidence for pentoxifylline plus vitamin E for reducing fibrosis in radiation-induced fibrosis combined pentoxifylline and vitamin E may reduce superficial radiation-induced fibrosis in women with radiation-induced fibrosis (level 3 [lacking direct] evidence)
 pentoxifylline and vitamin E may not reduce arm volume in women with long-standing radiation-induced fibrosis (level 3 [lacking direct] evidence)
long-pulsed dye laser at 585 nm or 595 nm may improve vessel clearance and pain in women with telangiectasia due to radiation therapy (level 2 [mid-level] evidence)
 for chronic ulcerations and wounds, consider general wound care measures and skin flaps or artificial bio-engineered skin for nonhealing ulcers
Prevention
Radiation Therapy-Related Prevention
 evolution in radiation techniques have helped prevent radiation dermatitis by delivering a more uniform, homogenous radiation dose three-dimensional (3-D) techniques reported to significantly reduce skin related toxicities
 field-in-field 3-D techniques or intensity-modulated radiation therapy (IMRT) allow for multiple smaller radiation fields
 show improved rates of hyperpigmentation, edema, and moist desquamation
 reported to reduce duration and severity of acute radiation dermatitis and long-term skin changes
 prone position in breast cancer radiation reported to improve breast dose homogeneity and acute dermatitis outcomes
 enables optimal dose distribution when combined with 3-D/IMRT techniques
 hypofractionation higher daily dose of radiation, which ultimately results in shorter treatment time (from 5-6 to 3-4 weeks)
 reported to improve dermatitis, pruritus, hyperpigmentation, and pain
 Reference – Breast Cancer (Dove Med Press) 2017;9:313full-text
compared to conventional fractionation, hypofractionated whole breast irradiation may reduce acute dermatitis in women with breast cancer undergoing radiation post breast-conserving surgery (level 2 [mid-level] evidence) based on 1 randomized trial with analyses of secondary outcomes and 1 cohort study
 287 women (median age 60 years) with pathologically confirmed carcinoma or invasive breast cancer, treated with breast-conserving surgery and whole breast irradiation (WBI) were randomized to hypofractionated WBI (HF-WBI) or conventionally fractionated WBI (CF-WBI) radiation included HF-WBI involved 42.56 Gy in 16 fractions of WBI
 CF-WBI involved 50 Gy in 25 fractions of WBI
 75% of women were non-Hispanic White patients
 28% of women were with overweight and 48% were with obesity
 comparing HF-WBI vs. CF-WBI median elapsed days of treatment 22 days vs. 36 days
 grade ≥ 2 acute toxicities (fatigue, pruritus, dermatitis, breast pain, hyperpigmentation) in 47% vs. 78% (p < 0.001 NNT 4)
 grade ≥ 1 pruritus in 54% vs. 81% (p < 0.001 NNT 4)
 grade ≥ 2 dermatitis in 36% vs. 69% (p < 0.001 NNT 3)
 grade ≥ 2 hyperpigmentation in 9% vs. 20% (p = 0.002 NNT 9)
 no significant differences in physician-assessed 6-month skin toxicities
 HF-WBI associated with less lack of energy at 6-month follow-up (odds ratio [OR] 0.39, 95% CI 0.24-0.63)
 less trouble meeting family needs (OR 0.34, 95% CI 0.16-0.75)
 Reference – JAMA Oncol 2015 Oct;1(7):931full-text, editorial can be found in JAMA Oncol 2015 Oct;1(7):941
 2,309 women (mean age 61 years) who received adjuvant whole breast radiation therapy after lumpectomy for unilateral breast cancer from October 2011 through June 2014 across academic and community radiation oncology practices across Michigan, United States, were assessed in a prospective cohort study 1,781 women had follow-up physician assessments completed at visits between 8 and 210 days after end of treatment
 1,723 women had completed at least comprehensive end-of-treatment questionnaire and at least 1 weekly questionnaire during treatment
 578 women received hypofractionated radiation and 1,731 received conventional fractionated radiation
 women who received hypofractionated radiation were older, had lower body mass index (BMI), smaller tumors, and less frequency of nodal involvement, nodal radiation treatment, and received chemotherapy
 comparing hypofractionated radiation vs. conventional fractionated radiation grade ≥ 2 radiation dermatitis in 27.4% vs. 62.6% (p < 0.001, NNT 3)
 skin induration in 13.7% vs. 21.1% (p = 0.01, NNT 8)
 moist desquamation in 6.6% vs. 28.5% (p < 0.001, NNT 5)
 dry desquamation in 18.7% vs. 58.8% (p < 0.001, NNT 3)
 burning or stinging of skin in 15.7% vs. 38.7% (p = 0.001, NNT 5)
 Reference – JAMA Oncol 2015 Oct;1(7):918, editorial can be found in JAMA Oncol 2015 Oct;1(7):941
compared to conventional radiation therapy, IMRT may reduce occurrence of moist desquamation and late telangiectasia in women undergoing postmastectomy radiation therapy (level 2 [mid-level] evidence) based on prospective cohort study
 242 women (mean age 51 years) who received postmastectomy radiation of chest wall, supra/infraclavicular, and internal mammary nodes by IMRT or conventional technique were followed for 2 years 106 women received IMRT and 138 women received radiation by conventional technique
 radiation dermatitis was assessed weekly from start until 4 weeks post radiation therapy, and telangiectasia was checked every 6 months for ≥ 2 years after completion of treatment
 comparing IMRT vs. conventional therapy grade 2 radiation dermatitis in 29.2% vs. 36.2% (not significant)
 moist desquamation in chest wall, other than axillary skin folds and creases in 13.2% vs. 35.5% (p < 0.001, NNT 5)
 grade 2 telangiectasia in 8.5% vs. 23.1% (p = 0.002, NNT 7)
 Reference – Oncotarget 2017 Oct 3;8(45):80012full-text
prone tangential field IMRT reduces development of moist desquamation compared to supine multibeam IMRT in women undergoing hypofractionated IMRT after breast-sparing surgery (level 2 [mid-level] evidence) based on randomized trial without assessor blinding
 100 women (mean aged 58 years) indicated for hypofractionated IMRT after breast-sparing surgery were randomized to prone tangential field vs. supine multibeam IMRT at a single center between December 2010 and October 2012
 comparing prone position vs. supine position moist desquamation in 6% vs. 20% (p = 0.04, NNT 7)
 grade 2/3 dermatitis in 38% vs. 80% (p < 0.001, NNT 3)
 confluent moist desquamation (grade 3 dermatitis) in 0% vs. 4% (no p value reported)
 grade 2 edema in 12% vs. 36% (p = 0.005, NNT 5)
 pain in 56% vs. 74% (p = 0.06)
 Reference – Radiother Oncol 2013 Aug;108(2):203
compared to WBI, accelerated partial breast irradiation (APBI) with multicatheter brachytherapy may reduce incidence of radiation dermatitis in women receiving radiation therapy post breast-conserving surgery for breast cancer based on randomized trial without intention to treat analysis
 1,328 women (median age 62 years) who had breast-conserving surgery for Union for International Cancer Control (UICC) stage 0-IIA breast cancer were randomized to receive APBI vs. WBI at multiple centers in Europe APBI was given at either 32 Gy/8 fractions, or 30.1 Gy/7 fractions (high-dose rate [HDR]-brachytherapy), or 50 Gy/0.60–0.80 Gy per pulse (pulsed-dose rate [PDR]-brachytherapy) and WBI was given at 50 Gy and a boost of 10 Gy
 follow-up was every 3 months for 2 years after surgery and then every 6 months in years 3-5 and then at 12-month interval
 comparing APBI vs. WBI grade 2 radiation dermatitis in 2% vs. 36% (p < 0.0001, NNT 3)
 grade 3 radiation dermatitis in 0.2% vs. 7% (p < 0.0001, NNT 15)
 grades 1-2 radiation dermatitis in 21% vs. 86% (p < 0.0001, NNT 2)
 mild hematomas in 20% vs. 2% (p < 0.0001, NNH 5)
 mild breast infection in 5% vs. 2% (p = 0.01, NNH 33)
 Reference – Radiother Oncol 2016 Jul;120(1):119
Self-Care
 daily hygiene recommendations from Skin Toxicity Study Group of the Multinational Association for Supportive Care in Cancer (MASCC) 2013 guidelines(4) gentle washing with water, with or without mild soaps or shampoos is recommended (MASCC Grade B)
 antiperspirant use is allowed, as evidence does not support any association between increased toxicity with antiperspirant use (MASCC Grade A)
 other general considerations for skin care(1,2,3) advise use of unscented, lanolin-free water-based moisturizers, and avoid metallic or oil-based topical products
 avoid exposure of treatment site to sun and temperature extremes
 use electric razor or clipper if shaving of treated area is required
 pat skin dry to avoid friction
 advise loose-fitted clothing over site of radiation to prevent friction
 in case of breast cancer, avoid underwire bras, and in case of radiation therapy to head and neck area, avoid wearing collars (Br J Nurs 2014 Feb 27-Mar 12;23(4):S28, S30)
 diet considerations avoid tobacco and alcohol
 if receiving radiation therapy to the throat, eat soft, mushy food that is easy to swallow
 maintain proper hydration and good oral health
 if receiving radiation therapy for bowel or gynecological cancers, consider increasing fiber intake in case of change in bowel movements
 if receiving radiation therapy to endometrium or rectum, at least 2 pints of water daily advised to lessen pain while urinating
 Reference – Br J Nurs 2014 Feb 27-Mar 12;23(4):S28, S30
moisturizers may not reduce risk of grade ≥ 2 acute radiation dermatitis in patients with breast cancer receiving radiation therapy (level 2 [mid-level] evidence) based on systematic review with wide confidence interval
systematic review of 6 randomized trials comparing standard moisturizers vs. control in 426 patients with breast cancer receiving radiation therapymoisturizers varied across trials and included aloe vera gel in 2 trials, emulsion of olive oil and calcium hydroxide in 1 trial, Lipiderm in 1 trial, heparinoid in 1 trial, and commercial moisturizing cream in 1 trial
control was no treatment in 5 trials and standard skin care in 1 trial
skin-related quality of life was assessed using Skindex-16, with higher scores indicating worse quality of life
pain was assessed on 100-point visual analog scale (VAS), with higher scores indicating more pain
no significant differences in risk ofgrade ≥ 2 acute radiation dermatitis in analysis of 5 trials with 377 patients, but CI includes possibility of benefit or harmrisk ratio 1.06 (95% CI 0.81-1.38)
consistent results for grade ≥ 3 acute radiation dermatitis in analysis of 5 trials with 361 patients
pruritus in 1 trial with 45 patients
moisturizers associated withimproved skin-related quality of life (mean Skindex-16 score 1.03 points with moisturizer vs. 2.73 points with control, p = 0.05) in 1 trial with 62 patients
nonsignificant reduction in pain (mean VAS score 5.7 points with moisturizer vs. 15.1 points with control, p = 0.06) in 1 trial with 45 patients
Reference – Breast Cancer 2023 Jan;30(1):2
Topical Corticosteroids
 prophylactic topical steroids to reduce discomfort and burning or itching of skin site are recommended by Skin Toxicity Study Group of the Multinational Association for Supportive Care in Cancer (MASCC) 2013 guidelines (MASCC Grade B)(4)
 consider application of low-to-medium potency topical corticosteroids 1-2 times daily for duration of radiation therapy(2)
 preparations used in trials include(2,4) mometasone furoate 0.1% cream
 hydrocortisone valerate 0.2% cream
 methylprednisolone 0.1% cream
 betamethasone 0.1% ointment
 beclomethasone spray 100 mcg/puff (2 puffs) twice daily
among patients with cancer receiving radiation therapy, topical corticosteroids may reduce risk of radiation dermatitis at completion of radiation therapy (level 2 [mid-level] evidence)based on systematic review with statistical limitations
systematic review of 6 randomized trials comparing topical corticosteroids vs. control in patients with cancer receiving radiation therapycorticosteroids included betamethasone in 5 trials (betamethasone administered twice daily in 4 trials and once daily in 2 trials) and mometasone once daily in 1 trial
control included supportive care, Essex cream, petrolatum, or no treatment
follow-up ranged from 1 week to 3 months
topical corticosteroids associated with reduced risk of radiation dermatitis at completion of radiation therapy (risk ratio [RR] 0.97, 95% CI 0.93-1) in analysis of 6 trials with 672 patients, but CI includes differences that may not be clinically important
no significant difference in radiation dermatitis at 3 weeks after radiation therapy (RR 0.68, 95% CI 0.31-1.5) in analysis of 4 trials with 394 patients, but CI includes possibility of benefit or harm
in subgroup analysistopical corticosteroids associated with reduced risk of radiation dermatitis at completion of radiation therapy in patients without chemotherapy compared to placebo group (RR  0.6, 95% CI 0.42-0.86) in analysis of 3 trials with 317 patients, but not in patients with chemotherapy compared to placebo RR 0.81, 95% CI 0.59-1.11) in analysis of 3 trials with 355 patients
topical corticosteroids twice daily associated with reduced risk of radiation dermatitis at completion of radiation therapy compared to placebo (RR 0.66, 95% CI 0.47-0.93) in analysis of 4 trials with 440 patients
topical corticosteroids once daily were not associated with reduced risk vs. placebo (RR 0.77, 95% CI 0.33-1.8) in analysis of 2 trials with 232 patients
Reference – Dermatol Ther 2022 Dec;35(12):e15918
prophylactic topical corticosteroids may reduce incidence of acute radiation dermatitis, specifically moist desquamation in women undergoing radiation therapy post modified radical mastectomy or breast conservation surgery (level 2 [mid-level] evidence) based on systematic review without significant difference in high-quality trial
 systematic review of 10 randomized control trials comparing steroids vs. nonsteroidal agents in 919 women with breast cancer undergoing radiation therapy after mastectomy or breast-conserving surgery
 radiation therapy dose ranged from 40 to > 56 Gy
 topical corticosteroids ranged from mild to potent and included beclomethasone, betamethasone, methylprednisolone, mometasone furoate, or hydrocortisone controls included cream, ointment, or liquid solution and 1 study had no treatment arm as control
 topical agents were applied 1-2 times daily from treatment initiation to completion and in some cases, up to 3 weeks post radiation therapy
 compared to control, topical corticosteroids associated with significant reduction in incidence of moist desquamation in analyses of 9 trials with 845 women odds ratio 0.29 (95% CI 0.19-0.45)
 NNT 6-10 with outcome in 22% of control group
 analyses included 2 high-quality trial with results nonsignificantly favoring topical corticosteroids
 mean acute radiation dermatitis score (standardized mean difference -0.47, 95% CI -0.61 to -0.33) in analyses of 9 trials with 806 women, results limited by significant heterogeneity
 patient-reported pruritus and burning symptoms in 4 trials with 406 women, and nonsignificant improvement in 2 trials with 252 women
 no significant difference in patient-reported pain in 4 trials with 344 women
 Reference – Anticancer Res 2017 Oct;37(10):5343full-text
mometasone furoate 0.1% during and 14 days after radiation therapy may reduce moist desquamation in patients receiving postmastectomy radiation therapy (level 2 [mid-level] evidence) based on randomized trial without intention-to-treat analysis
 143 patients (median age 48 years) with breast cancer, an Eastern Cooperative Oncology Group status of 0/1, and receiving postmastectomy radiation therapy were randomized to mometasone furoate 0.1% vs. Eucerin original cream applied twice daily for 5 weeks of radiation therapy and 14 days post therapy 35% had pathologic stage III disease, 6% had cT4d disease, and 68% had immediate reconstructive surgery
 124 patients included in analyses
 overall rate of moist desquamation 54.8%
 comparing mometasone furoate vs. Eucerin cream moist desquamation in 43.8% vs. 66.7% (p = 0.012 NNT 5)
 grade 3 radiation dermatitis in 18.8% vs. 33.3% (p = 0.036 NNT 7)
 median duration to develop grade 3 acute radiation dermatitis 35.5 days vs. 46 days (p < 0.001)
 no significant differences in patient reported outcomes assessed using the Skindex-16 scale comparing mometasone furoate vs. Eucerin cream
 development of moist desquamation associated with body mass index > 30 (hazard ratio [HR] 1.09, 95% CI 0.99-1.19)
 use of Eucerin skin cream (HR 2.21, 95% CI 0.93-5.25)
 dosimetric variable V110 (HR 1.03, 95% CI 1.01-1.06)
 Reference – Int J Radiat Oncol Biol Phys 2018 Jun 1;101(2):325
Topical Antibacterials
bacterial decolonization with mupirocin ointment plus chlorhexidine body cleanser may reduce risk of grade ≥ 2 acute radiation dermatitis with moist desquamation in adults with breast cancer receiving photo-beam radiation therapy (level 2 [mid-level] evidence) based on randomized trial with protocol amendment
80 adults with diagnosis of breast cancer or head and neck cancer and plans for photo-beam radiation therapy for cure were randomized to bacterial decolonization vs. standard care throughout radiation therapybacterial decolonization included intranasal mupirocin ointment 2% twice daily plus chlorhexidine gluconate body cleanser 4% once daily for 5 days before radiation therapy and repeated for 5 days every 2 weeks for duration of radiation therapy
standard care included normal hygiene and emollients
primary outcome was changed from any grade ≥ 2 acute radiation dermatitis to grade ≥ 2 acute radiation dermatitis with moist desquamation after interim analysis, due to wide variability in clinical presentation on blinded review
77 patients (mean age 59 years, 97% female) completed radiation therapy and were included in analysis75 patients had breast cancer, 2 had head and neck cancer
Staphylococcus aureus incidence 10.8% in bacterial colonization group vs. 16.2% in standard care group
adherence to regimen was 69% in bacterial colonization group
comparing bacterial decolonization vs. standard care at end of treatmentrates of grade ≥ 2 acute radiation dermatitis with moist desquamation0% vs. 23.7% (p = 0.001, NNT 5) overall
0% vs. 21.6% (p = 0.002, NNT 5) in prespecified subgroup of patients with breast cancer
S. aureus incidence 5.4% vs. 24.3% (p = 0.02)
mean acute radiation dermatitis grade 1.2 vs. 1.6 (p = 0.02)
no significant difference between groups in risk of any grade ≥ 2 acute radiation dermatitis (original primary outcome)
1 person in bacterial colonization group withdrew from trial due to itching
Reference – JAMA Oncol 2023 Jul 1;9(7):940
Nonsteroidal Topical Agents
 recommendations for nonsteroidal topical agents for prevention of radiation dermatitis from Skin Toxicity Study Group of the Multinational Association for Supportive Care in Cancer (MASCC) 2013 guidelines(4) weak recommendation supporting the use of silver sulfadiazine 1% cream in breast cancer (MASCC Grade B)
 strong recommendation against the use of aloe vera (MASCC Grade A)
 trolamine (MASCC Grade A)
 weak recommendation against silver leaf dressing (MASCC Grade C)
 insufficient evidence to support use of any of following sucralfate and derivatives (MASCC Grade C)
 hyaluronic acid or hyaluronic acid-based combinations
 ascorbic acid (MASCC Grade C)
 petroleum-based ointments (MASCC Grade C)
 Theta-Cream (MASCC Grade C)
 dexpanthenol (MASCC Grade C)
prophylactic application of heparinoid moisturizer during radiation therapy and continued until 3 months post therapy may reduce development of desquamation in women with breast cancer (level 2 [mid-level] evidence) based on small randomized trial without blinding and placebo control
 48 women (aged between 30 and 65 years) with breast cancer undergoing whole breast radiation therapy post lumpectomy were randomized to prophylactic application of heparinoid moisturizer vs. no moisturizer
 heparinoid moisturizer was applied from first day of radiation therapy twice daily until 3 months after completion of radiation therapy
 compared to no moisturizer, prophylactic application of heparinoid moisturizer associated with significantly lower desquamation from last day of radiation until 3 months after radiation therapy (p < 0.05)
 lower skin dryness from last day until 4 weeks following radiation therapy (p < 0.05)
 Reference – Jpn J Clin Oncol 2018 May 1;48(5):450full-text
addition of silver sulfadiazine 1% cream to general skin care may reduce severity of radiation dermatitis in women with breast cancer undergoing radiation therapy after mastectomy and chemotherapy (level 2 [mid-level] evidence) based on randomized trial without placebo control
 104 women (mean age 48 years) with breast cancer referred for radiation therapy post modified radical mastectomy and 6-8 courses of chemotherapy were randomized to topical silver sulfadiazine 1% cream plus general skin care vs. general skin care alone during radiation therapy radiation dose of 10 Gy was applied in single fractions of 200 cGy/day 5 times weekly (Saturday to Wednesday) for 5 weeks
 silver sulfadiazine applied to irradiated field every 8 hours for 3 consecutive days starting on Wednesday ≥ 2 hours after radiation treatment, and continued for 5 weeks of radiation therapy and 1 week after
 general skin care included gentle washing with baby soap, patting area dry, wearing loose cotton clothes, and no use of cosmetics, perfume, cologne, or deodorant
 comparing silver sulfadiazine cream plus general skin care vs. general skin care alone total score of skin injury of 5.49 vs. 7.21 (p < 0.001)
 grade 3 dermatitis in fifth week in 3.9% vs. 19.6% (p = 0.002, NNT 7)
 grade 3 dermatitis in sixth week in 21.5% vs. 52.9% (p = 0.001, NNT 4)
 flat chest wall anatomy significantly associated with decreased severity of dermatitis (p = 0.008)
 Reference – Support Care Cancer 2012 Aug;20(8):1613
topical calendula might be effective for prophylaxis of radiation-induced dermatitis in women with breast cancer (level 2 [mid-level] evidence) based on Cochrane review with limited evidence
 systematic review of 8 randomized trials evaluating homeopathic medicines for preventing or treating symptoms associated with cancer treatments in 664 patients
 3 trials with 402 patients evaluated effect of homeopathy on adverse effects of radiation therapy topical calendula more effective than trolamine (topical agent containing corticosteroids) for prevention of radiation therapy-induced dermatitis in 1 high-quality trial with 254 women with nonmetastatic breast cancer
 homeopathic Cobaltum 30C and Causticum 30C evaluated in 1 trial with unclear risk of bias and data not suitable for analysis
 Belladonna 7C twice daily and x-ray 15C once daily not associated with significant effect on severity of skin reactions during radiation therapy in 1 trial of 66 women with breast cancer who had quadrantectomy and axillary dissection, homeopathy reported to reduce severity during recovery
 no serious adverse effects or interactions associated with homeopathy
 Reference – Cochrane Database Syst Rev 2009 Apr 15;(2):CD004845
topical Chinese herbal medicine may reduce severity of radiation dermatitis compared to routine drugs or standard therapy in patients without any type of dermatitis or skin lesions starting radiation therapy for cancer (level 2 [mid-level] evidence) based on systematic review limited by possible publication bias
systematic review of 38 randomized trials evaluating topical Chinese herbal medicine for prevention of radiation dermatitis in 3,439 patients without any type of dermatitis or skin lesions starting radiation therapy for cancerprinciple of topical Chinese herbal medicine was based on heat clearance, supplemented by replenishing qi and nourishing yin, activating blood, resolving stasis, and relieving pain
comparators included routine drugs in 18 trials and standard therapy in 20 trials
types of cancers were mostly breast cancer and head and neck cancer
radiation dose ranged from 45 to 80 Gy
severity of radiation dermatitis was assessed using Radiation Therapy Oncology Group (RTOG) grading criteria
publication bias was inferred based on asymmetry in funnel plots of trials evaluating topical Chinese herbal medicine for incidence and severity of radiation dermatitis
comparing topical Chinese herbal medicine to routine drugstopical Chinese herbal medicine associated withreduced severity of radiation dermatitis in analysis of 18 trials with 1,584 patientsrisk ratio (RR) 0.46 (95% CI 0.35-0.6)
NNT 6-9 with reduced severity in 29% of routine drug group
decreased skin and mucosa recovery time (mean difference [MD] -2.35 days, 95% CI -3.58 to -1.12 days) in analysis of 4 studies with 301 patients
delayed occurrence of radiation dermatitis (MD 2.36 days, 95% CI 1.74-2.98 days) in analysis of 4 studies with 334 patients
improved quality of life in analysis of 2 trials with 186 patientsRR 1.46 (95% CI 1.03-2.06)
NNT 3-108 with improved quality of life in 31% of routine drug group
no significant difference in incidence of radiation dermatitis (RR 0.99, 95% CI 0.97-1.01) in analysis of 18 trials with 1,584 patients, results limited by significant heterogeneity
comparing topical Chinese herbal medicine to conventional therapy, topical Chinese herbal medicine associated with reduced severity of radiation dermatitis in analysis of 19 trials with 1,703 patientsRR 0.28 (95% CI 0.21-0.38)
NNT 5-6 with reduced severity in 27% of conventional therapy group
adverse events included rash in smeared area in 1 patient in topical Chinese herbal medicine group in 1 trial
Reference – Front Pharmacol 2022;13:819733
compared to baby oil, prophylactic use of sandalwood oil-turmeric lotion might reduce incidence and severity of dermatitis in women with breast cancer undergoing radiation therapy (level 2 [mid-level] evidence) based on small randomized trial without patient blinding
 40 women (mean age 49 years) who had unilateral breast cancer and referred for radiation therapy after undergoing radical mastectomy and adjuvant chemotherapy were randomized to sandalwood oil-turmeric based lotion (VICCO) vs. baby oil radiation target dose of 50 Gy was applied at ≤ 1 fraction of 2 Gy/day 5 times weekly, at same time of day for 7 consecutive weeks
 cream or oil applied 5 times daily including 2 hours before, immediately after, 2 hours after, 4 hours after, and 6 hours after radiation therapy for 7 weeks during therapy and 2 weeks after
 comparing sandalwood oil-turmeric based lotion vs. baby oil grade 1 dermatitis at end of week 2 in 32% vs. 75% (p = 0.025, NNT 2)
 no development of dermatitis in 15% vs. 5% (no p value reported)
 sandalwood oil-turmeric lotion use associated with significantly lower incidence of grade 2 and grade 3 dermatitis at week 3 and week 4
 significantly reduced degree and severity of dermatitis at weeks 2, 3, and 4
 Reference – Medicines (Basel) 2017 Jun 24;4(3)full-text
CLINICIANS’ PRACTICE POINT: Expert opinion commonly advises against the use of fragrance applications due to the potential risk for allergic or irritant contact dermatitis; patients in this study were patch-tested with sandalwood oil-turmeric based lotion prior to inclusion in this study.
 aloe veraaloe vera may reduce risk of radiation dermatitis in patients with cancer having radiation therapy (level 2 [mid-level] evidence) based on systematic review limited by heterogeneity
systematic review of 14 randomized trials comparing application of aloe vera vs. placebo or no aloe vera in 1,572 patients with cancer having radiation therapymean patient age ranged from 46 to 56 years
aloe vera applications were fresh, gel, cream, or lotion formulations
total radiation dose ranged from 2,000 to 7,000 Gy
trial duration ranged from 2 to 10 weeks where reported
types of cancers mostly included nasopharyngeal carcinoma and breast cancer
aloe vera associated with reduced risk of radiation-induced dermatitis in analysis of all trials, results limited by significant heterogeneityrisk ratio 0.76 (95% CI 0.76-0.88)
NNT 5-12 with radiation-induced dermatitis in 73% of no aloe vera or placebo group
consistent results in patients with grade 2 and 3 radiation-induced dermatitis; nonsignificant reduction seen in patients with grade 4 radiation-induced dermatitis
Reference – Front Pharmacol 2022;13:976698full-text
Barrier Products
 barrier products include spray on barrier films like 3M Cavilon No-Sting Barrier Film and Mepitel Film
 reported to reduce rates of moist desquamation, pain, and pruritus but evidence is limited
 Reference – Breast Cancer (Dove Med Press) 2017;9:313full-text
semi-permeable dressings may be effective in preventing acute radiation dermatitis in patients receiving radiation therapy for cancer (level 2 [mid-level] evidence) based on systematic review without meta-analyses
 systematic review of 6 randomized trials between 2010 and 2014 evaluating semi-permeable dressings in management of radiation dermatitis in 504 patients receiving radiation therapy for cancer 3 trials evaluated Mepilex Lite
 1 trial evaluated Mepitel Film
 2 trials evaluated silver nylon dressings
 compared to control (aqueous cream or wound cleansing with salted water), Mepilex Lite or Mepitel Film application associated with significant improvement in pain, discomfort, itchiness, and burning in 2 trials with 98 patients with breast cancer and 1 trial with 88 patients with nasopharyngeal cancer
 sleep in 1 trial with 88 patients with nasopharyngeal cancer
 compared to aqueous cream, Mepitel Film associated with significantly reduced skin reactions and moist desquamation in 1 trial with 80 patients with breast cancer (summarized here)
 compared to standard skin care, prophylactic silver clear nylon dressing significantly reduced radiation dermatitis score in 1 trial with 42 patients with anal canal or rectal cancer
 no significant difference in development of moist desquamation, inframammary fold toxicity, pain, or burning between group treated with silver leaf nylon dressing vs. control group in 1 trial with 196 patients
 Reference – Eur J Cancer Care (Engl) 2017 Nov;26(6):doi:10.1111/ecc.12685
prophylactic use of Mepitel Film may reduce moist desquamation in adults receiving radiation therapy for breast cancer based on randomized intrapatient control trial
 80 adults (mean age 59 years, 97.4% women) receiving radiation for breast cancer were enrolled and lateral and medial halves of the skin areas were randomized to Mepitel Film vs. aqueous cream
 comparing Mepitel Film treated area vs. aqueous cream treated area acute radiation dermatitis in 44% vs. 100% (no p value reported)
 moist desquamation in 0% vs. 26% (p < 0.001)
 Mepitel Film associated with 92% reduction in skin reaction severity scored using Radiation-Induced Skin Reaction Assessment Scale (RISRAS) (p < 0.001)
 Reference – Radiother Oncol 2014 Jan;110(1):137
prophylactic application of Hydrofilm polyurethane film dressings may reduce severity of radiation dermatitis in women with breast cancer (level 2 [mid-level] evidence) based on randomized intrapatient control trial
 62 women (median age 62 years) with breast cancer receiving radiation therapy post breast-conserving surgery were enrolled and lateral and medial halves of the skin areas were randomized to Hydrofilm or 5% urea lotion
 6 women stopped applying Hydrofilm due to itching, redness of skin, or allergic eczema
 comparing Hydrofilm area vs. 5% urea lotion area mean Radiation Therapy Oncology Group/European Organization for Research and Treatment of Cancer (RTOG/EORTC) score for radiation dermatitis severity of 0.35 vs. 1.33 (p < 0.001)
 moist desquamation in 0% vs. 10.7%
 mean itching score of 0.32 vs. 1 (p < 0.001)
 mean pain score of 0.44 vs. 0.83 (p = 0.04)
 adverse reactions of Hydrofilm included localized maculopapular rash in 8.1%
 reactions related to shear stress on skin at edges of dressing due to inaccurate placement of dressing, including redness in 19.4%, mild itching in 16.1%, burning in 11.3%, and blisters in 6.5%
 Reference – Acta Oncol 2018 Jul;57(7):908
application of hydroactive colloid gel during radiation therapy may reduce incidence and delay onset of moist desquamation in women undergoing radiation therapy post surgery (level 2 [mid-level] evidence) based on cohort study
 222 women (mean age 56 years) indicated for radiation therapy post breast-sparing surgery applied hydroactive colloid gel to irradiated area prior to irradiation and were compared to 2 groups of matched historical cohorts historical cohorts included patients using dexpanthenol cream until days 11-14, then hydroactive colloid gel till end of treatment
 patients using dexpanthenol 5% cream throughout radiation therapy
 moist desquamation in first 25 fractions of radiation therapy in 6.9% with hydroactive gel vs. 35.1% with dexpanthenol only (p < 0.001, NNT)
 preventive hydroactive gel associated with significantly longer time to onset of moist desquamation compared to dexpanthenol group (hazards ratio 5.95, 95% CI 3.26-10.86)
 no significant difference between hydrogel only and dexpanthenol cream followed by hydroactive gel for incidence of moist desquamation and probability of moist desquamation free survival
 moist desquamation associated with larger breast size (odds ratio 1.31, 95% CI 1.18-1.44)
 Reference – Eur J Oncol Nurs 2017 Aug;29:1
Systemic Therapy
 insufficient evidence to recommend for or against use of the following systemic therapies, from Skin Toxicity Study Group of the Multinational Association for Supportive Care in Cancer (MASCC) 2013 guidelines(4) oral hydrolytic enzyme (Wobe-Mugos E.), a proteolytic enzyme mixture of 100 mg papain, 40 mg trypsin, and 40 mg chymotrypsin reported to have analgesic and anti-inflammatory effects (MASCC Grade B)
 zinc supplementation (MASCC Grade C)
 pentoxifylline (MASCC Grade C)
prophylactic enteral glutamine may reduce radiation dermatitis in patients with breast cancer based on small randomized trial
 40 patients (mean age 46-50 years) with breast cancer receiving radical radiation therapy post modified radical mastectomy or breast-conserving surgery were randomized to receive glutamine 15 g/day orally in 3 divided doses vs. placebo glutamine (prepared in 250 mL water at room temperature) was started 1 week prior to radiation therapy and continued until 1 week after
 placebo group received oral glucose solution
 comparing glutamine group vs. placebo group grade 1 acute radiation dermatitis in 89% vs. 0% (p < 0.001, NNT 1)
 grade 2 acute radiation dermatitis in 11% vs. 80% (p < 0.001, NNT 2)
 grade 3 acute radiation dermatitis in 0% vs. 20% (p < 0.001, NNT 5)
 no adverse effects associated with glutamine reported
 Reference –Clin Nutr 2016 Apr;35(2):436
pentoxifylline and vitamin E reported to prevent radiation-related capsular contraction of breast implants following mastectomy, immediate reconstruction, and adjuvant radiation therapy in women with breast cancer (level 3 [lacking direct] evidence) based on uncontrolled clinical trial
 26 women (mean age 47 years) with breast cancer treated by mastectomy and immediate reconstructive surgery who required adjuvant radiation therapy after reconstruction were given pentoxifylline 400 mg orally 3 times daily and vitamin E 400 units orally twice daily starting ≤ 4 weeks of completion of radiation and continued for 6 months
 follow-up continued for 12 months after pentoxifylline and vitamin E were stopped
 surgical revision of implant due to capsular contraction needed in 2 women (7.7%)
 no loss of implants reported (historic comparison of 18.6% in similar patients not given pentoxifylline and vitamin E reported)
 Reference – Am J Surg 2016 May;211(5):854
combined pentoxifylline and vitamin E might prevent development of radiation-induced fibrosis in patients with breast cancer (level 3 [lacking direct] evidence) based on nonclinical outcomes from randomized trial
 53 patients with breast cancer undergoing radiation therapy post breast-conservation surgery or mastectomy were randomized to treatment with pentoxifylline 400 mg orally 3 times daily and vitamin E 400 units orally once daily for 6 months vs. standard care after radiation with follow-up for 18 months post radiation
 breast tissue compliance was compared in irradiated and untreated breast/chest wall in treatment and control group at 18 months using a tissue compliance meter (TCM) at 18 months
 comparing pentoxifylline plus vitamin E group vs. standard care mean difference in TCM measurement of 0.88 mm vs. 2.1 mm (p = 0.0478)
 median difference in TCM measurement of 1 mm vs. 2.4 mm (p = 0.0478)
 no significant differences in overall survival and disease-free survival at 5 years, Subjective, Objective, Management, and Analytic (SOMA) score, RTOG late morbidity scores, pain, and arm edema between groups
 Reference – Int J Radiat Oncol Biol Phys 2013 Mar 1;85(3):604
oral curcumin during and until 1 week post radiation therapy may not reduce radiation dermatitis severity in women with breast cancer (level 2 [mid-level] evidence) based on randomized trial with baseline differences
 686 women (mean age 58 years) with noninflammatory breast cancer receiving radiation therapy were randomized to curcumin 500 mg 4 capsules 3 times daily (total of 6 g/day) vs. placebo during and until 1 week post radiation therapy
 at baseline, previous chemotherapy in 37.2% with curcumin vs. 45.3% with placebo (p = 0.04)
 84.3% completed the study
 comparing curcumin vs. placebo moist desquamation in 9.54% vs. 12.2% (not significant)
 > grade 3 acute radiation dermatitis in 7.4% vs. 12.9% (not significant)
 no significant differences in patient-reported symptoms and quality of life
 Reference – Support Care Cancer 2018 May;26(5):1543
oral celecoxib during and after radiation therapy may reduce radiation therapy-induced itching and pain, but not incidence of dermatitis in patients with breast cancer (level 2 [mid-level] evidence) based on small randomized trial
 60 patients with breast cancer were randomized to oral celecoxib 400 mg/day vs. placebo capsules during radiation therapy
 oral celecoxib use during and after radiation therapy associated with significant reduction in radiation-induced itching
 significant reduction in radiation therapy-induced pain
 no significant difference in dermatitis
 Reference – Antiinflamm Antiallergy Agents Med Chem 2018;17(1):57
Laser Therapy
 insufficient evidence to recommend for or against use of light-emitting diode (LED) laser therapy for prevention of radiation dermatitis, from Skin Toxicity Study Group of the Multinational Association for Supportive Care in Cancer (MASCC) 2013 guidelines (MASCC Grade C)(4)
photobiomodulation laser therapy (PBMT) applied immediately after each radiation therapy session may prevent development of ≥ grade 2 radiation dermatitis in women with breast cancer (level 2 [mid-level] evidence) based on randomized trial without intention to treat analysis
 139 women (mean age 56 years) with breast cancer undergoing identical radiation therapy regimen post lumpectomy were randomized to PBMT vs. placebo after each radiation therapy session patients received laser therapy or placebo 2 times weekly for a total of 14 sessions
 all patients also received institutional standard skin care that included application of a topical, hydroactive colloid gel and in case of acute skin reactions, received self-adhesive silicone dressings on irradiated zones
 PBMT was delivered using a class IV MLS 1 M6 laser that combines 2 synchronized laser diodes in the infrared range (808– 905 nm) with a fixed energy density (4 joule/cm2)
 19 patients lost to follow-up and not included in analyses
 outcome measures included Radiation-Induced Skin Reaction Assessment Scale (RISRAS) score consists of a health professional score (0–24) based on the outward signs of skin reaction and a patient score (0–12) based on the patients’ personal experience of skin reactions (pain, burning sensation, itchiness, and quality of life) with higher scores indicating greater toxicities
 quality of life was assessed using Skindex-16 score, a 16-item self-assessment questionnaire based on symptoms, emotions, and functioning rated on a scale from 0 (never bothered) to 6 (always bothered)
 comparing laser therapy vs. placebo ≥ grade 2 radiation dermatitis at end of radiation therapy in 6.7% vs. 30% (p = 0.004, NNT 5)
 grade 3 radiation dermatitis at end of radiation therapy in 0% vs. 3% (no p value reported)
 compared to placebo, laser therapy associated with significantly lower subjective RISRAS scores
 total Skindex-16 scores
 Reference – Lasers Surg Med 2018 Feb 10 early online
Treatment
Acute Radiation Dermatitis
 for mild (grade 1) reactions, options include(2) nonspecific treatment similar to prevention measures
 consider hydrophilic moisturizers for dry desquamation
 consider low-to-medium potency topical steroids for pruritus and irritation, such as any of the following mometasone furoate 0.1% cream
 hydrocortisone valerate 0.2% cream
 methylprednisolone 0.1% cream
 betamethasone 0.1% ointment
 beclomethasone spray 100 mcg/puff (2 puffs) twice daily
 for moderate (grade 2 and 3) reactions(1,2,3,4) for moist desquamation, consider measures to prevent secondary infection
 consider wound care measures to maintain moist wound environment to allow for re-epithelialization, including any of the following dressings (MASCC Grade C) hydrogel dressings
 hydrocolloid dressings
 silver clear nylon dressings
 for severe (grade 4) reactions(2) consider stopping radiation therapy until skin heals completely
 consider a multidisciplinary approach with surgical debridement to remove necrotic debris and reconstruction with skin flaps
Chronic Radiation Dermatitis – Treatment
Radiation-Induced Fibrosis
 consider a multidisciplinary approach with wound care management, physical therapy, and pain management(2,5) consider active and passive physical therapy to reduce contractions and increase mobility
LPG mechanical massage after completion of radiation therapy associated with decrease in skin induration and increase in skin softness in women who had undergone breast-conserving surgery followed by radiation therapy (level 2 [mid-level] evidence) based on prospective cohort study
 20 women (mean age 49 years) who had breast-conserving surgery followed by radiation therapy > 6-16 months prior were randomized to LPG technique vs. medical supervision for 1 month LPG technique of mechanical massage allows skin mobilization by folding and unfolding
 10-minute treatment was applied every other day, 3 times weekly for 1 month
 evaluations were done at enrollment, after 15 sessions of LPG treatment (T1), or 1 month after end of LPG treatment (T2)
 LPG treatment associated with decrease in skin induration (p = 0.003)
 increase in skin softness (p = 0.0062)
 Reference – Skin Res Technol 2008 Feb;14(1):71
 therapy using deep friction massage reported to reduce muscle spasm related to radiation-induced fibrosis (RIF) in woman aged 57 years with breast cancer treated with adjuvant radiation, in case report (Integr Med (Encinitas) 2014 Oct;13(5):32full-text)
 pentoxifylline for radiation-induced telangiectasia and fibrosis, Multinational Association for Supportive Care in Cancer (MASCC) panel makes a weak recommendation against the use of pentoxifylline for the reduction of fibrosis in standard clinical practice (MASCC Grade B)(2,3,4)
 for established RIF, MASCC panel suggests pentoxifylline for reducing fibrosis(4)
combined pentoxifylline and vitamin E may reduce superficial RIF in women with RIF (level 3 [lacking direct] evidence) based on nonclinical outcome in small randomized trial
 24 women (mean age 57 years) with clinically measurable RIF were randomized to 1 of 4 treatment groups pentoxifylline 800 mg/day plus vitamin E 1,000 units/day
 pentoxifylline 800 mg/day plus placebo
 placebo plus vitamin E 1,000 units/day
 placebo plus placebo
 clinical regression of RIF defined as centripetal reduction of edges of fibrotic block in all RIF areas documented, without any RIF contraction
 comparing pentoxifylline plus vitamin E vs. placebo only group at 6 months mean RIF surface regression of 60% vs. 43% (p = 0.038)
 mean RIF volume regression of 73% vs. 51% (p = 0.054)
 Subjective, Objective, Management, and Analytic (SOMA) score for symptom severity 39% vs. 33% (not significant)
 Reference – J Clin Oncol 2003 Jul 1;21(13):2545
pentoxifylline and vitamin E may not reduce arm volume in women with long-standing RIF (level 3 [lacking direct] evidence) based on nonclinical outcome in randomized trial
 68 patients with breast cancer and ≥ 20% increase in arm volume at a median 15.5 years (range 2-41 years) after axillary/supraclavicular radiation therapy randomized to pentoxifylline 400 mg orally twice daily plus dl-alpha tocopheryl acetate 500 mg orally twice daily vs. placebos for 6 months with follow-up to 12 months
 no significant difference in mean change in arm volume (primary outcome), tissue fibrosis of breast or chest wall, pectoral fold or supraclavicular fossa, photographic breast/chest wall appearance, or patient self-assessment of function and quality of life
 Reference – Radiother Oncol 2004 Nov;73(2):133
 insufficient evidence for use of following agents in treatment of fibrosis(2,5) superoxide dismutase
 interferon gamma
 hyperbaric oxygen therapy
 laser therapy with epidermal grafting
addition of hyperbaric oxygen therapy to standard care may not reduce patient-reported moderate or severe pain in breast, chest wall, or shoulder (level 2 [mid-level] evidence), but may reduce moderate or severe fibrosis (level 3 [lacking direct] evidence) in patients with breast cancer and mild, moderate, or severe edema, fibrosis, or movement restriction ≥ 12 months after breast irradiationbased on clinical and nonclinical outcomes in randomized trial with low adherence
186 female patients (median age 60 years) with breast cancer and moderate or severe pain in breast, chest wall, or shoulder combined with mild, moderate, or severe edema, fibrosis, or movement restriction ≥ 12 months after breast irradiation were randomized to offer of hyperbaric oxygen therapy (HBOT) plus standard care vs. standard care alone and followed for 6 months
HBOT consisted of30-40 sessions of being seated in hyperbaric chamber (2 hours per session) delivered over 6-8 consecutive weeks
after pressure was increased to 2.5 atmospheres absolute, patients breathed 100% oxygen through mask during 4 intervals of 20 minutes, following which pressure was decreased to standard atmosphere
key inclusion criteria were completion of primary breast cancer treatment with curative intent (except for hormonal therapy) and no metastatic disease or recurrent breast cancer
primary outcome was patient-reported moderate or severe pain in breast, chest wall, or shoulder at 6 months, with treatment effectiveness defined as reduction to no or mild pain in breast, chest wall, or shoulder
25% of patients in HBOT group accepted and completed treatment, 90% were included in primary outcome analysis
power calculation was based on HBOT acceptance rate 50%, but observed rate was 25%
comparing HBOT plus standard care vs. standard care alone at 6 monthsmoderate or severe pain in breast, chest wall, and/or shoulder in 50% vs. 62% (odds ratio 0.63, 95% CI 0.32-1.23), not significant, but CI includes possibility of benefit or harm
moderate or severe fibrosis in 33% vs. 51% (p = 0.02, NNT 6) among 156 patients
breast edema in 11% vs. 21% (not significant) among 166 patients
movement restriction in 13% vs. 17% (not significant) among 166 patients
no significant difference in quality of life at 6 months
in sensitivity analysis of patients who completed HBOT, HBOT associated with decreased moderate or severe pain in breast, chest wall, and/or shoulder at 6 months (adjusted odds ratio 0.31, 95% CI 0.12-0.78)
among patients completing HBOT, adverse events included oxygen toxicity (100%), hypoglycemia (97%), ear barotrauma (87%), transient myopia (13%), and fatigue (3%)
Reference – HONEY trial JAMA Oncol 2024 Apr 1;10(4):464, editorial can be found in JAMA Oncol 2024 Apr 1;10(4):437
 review of radiation-induced fibrosis mechanisms and implications for therapy can be found in J Cancer Res Clin Oncol 2015 Nov;141(11):1985full-text
Telangiectasia
 long-pulsed dye laser (PDL) at 585 nm or 595 nm may be beneficial in treatment of radiation-induced telangiectasia(2,3,4,5)
 weak recommendation for use of long-PDL for telangiectasias (MASCC Grade B)(4)
long-PDL may improve vessel clearance and pain in women with telangiectasia due to radiation therapy (level 2 [mid-level] evidence) based on small intrapatient randomized trial
 13 women (mean age 51 years) with telangiectasias due to prior radiation therapy for breast cancer received a series of 3 treatments at 6-week intervals with long-PDL for half lesion and with intense pulsed light (IPL) for the other half of lesion intense pulsed light emitted light of wavelength band from 530 to 750 nm (PR applicator) and from 555 to 950 nm (VL applicator)
 long-PDL set at 595 nm
 comparing long-PDL vs. IPL median vessel clearance of 90% vs. 50% (p = 0.01)
 median visual analog scale pain score of 4.3 points vs. 6 points (p < 0.01)
 median visual analog scale satisfaction score of 8 points vs. 7 points (p < 0.05)
 9 patients preferred long-PDL over IPL
 Reference – Br J Dermatol 2009 Jun;160(6):1237
pulsed dye laser reported to improve quality of life and result in > 50% clearance of postradiation-induced telangiectasia in women with prior breast cancer based on 2 case series
 22 women (mean aged 56 years) with radiation-induced telangiectasia after treatment for breast cancer (mean 7.7 years after radiation treatment) were treated with pulse dye laser 595 nm PDL at 4- to 6-week intervals 6 patients lost to follow-up prior to > 50% clearance of radiation-induced telangiectasia
 ≥ 50% clearance of radiation-induced telangiectasia in 11 patients after 1 treatment session, and all 16 reported ≥ 50% clearance of radiation-induced telangiectasia by 4 sessions
 quality of life scores by Skindex-16 and Breast-Q Adverse Effects of Radiation significantly improved compared to baseline (p < 0.05)
 Reference – Lasers Surg Med 2018 Apr;50(4):284
 11 women (mean age 48 years) with radiation-induced telangiectasia after treatment for breast cancer were treated with pulse dye laser for an average of 3.9 years after completing radiation 9 women received 595 nm PDL and 2 received 585 nm for a mean number of 4.3 treatments
 mean clinical clearance of telangiectasia of 72.7% and all women reported improved sense of confidence and satisfaction with aesthetic appearance
 Reference – J Clin Aesthet Dermatol 2014 Dec;7(12):34full-text
 complications of cutaneous ulceration and breast implant compromise after pulsed dye laser treatment for telangiectasias at site of prior radiation and breast reconstruction reported in woman with history of breast cancer, in case report (JAAD Case Rep 2017 May;3(3):180)
 consider the following to avoid complications of pulsed dye laser focus treatment only in cosmetically sensitive areas like upper chest
 avoid areas of skin that received highest radiation dose
 avoid areas with thin tissue coverage
 use conservative laser settings
 Reference – JAAD Case Rep 2017 May;3(3):180full-text
Chronic Ulcerations and Wounds
 consider biopsy of suspicious ulcers to rule out secondary skin cancers(2,5)
 consider general wound care measures, including(2,5) wound dressings to protect skin
 hydrophilic or lipophilic creams and ointments with or without dressings to serve as barriers
 silver based dressings could potentially also serve as antibacterial agents
 surgical debridement for chronic ulcers
 consider skin flaps or artificial bio-engineered skin for nonhealing ulcers(2,5)
Prognosis
 radiation dermatitis can result in(3) functional impairment
 reduced quality of life
 reduced aesthetic appeal
 severe acute radiation dermatitis (grade 4) may require delaying further radiation therapy until the skin lesions completely heal(1,3)
 radiation-induced fibrosis and chronic radiation dermatitis may lead to lymphedema and reduced shoulder motion in patients with breast cancer
 for patients with breast cancer undergoing immediate reconstruction, radiation-induced fibrosis may lead to reconstruction failure and implant loss
 in patients with head and neck cancer, fibrosis can lead to trismus
 References – Am J Surg 2016 May;211(5):854 and J Cancer Res Clin Oncol 2015 Nov;141(11):1985full-text
 radiation-induced subsequent malignancies(1) cancers, such as basal cell carcinomas, keratoacanthomas, squamous cell carcinomas, or angiosarcomas may be diagnosed in radiated field many years after radiation therapy
 may be associated with younger age at time of radiation exposure
radiation dermatitis may impact skin-related quality of life in women with breast cancer based on cohort study
 40 women (mean age 40 years) having whole breast three-dimensional conformal radiation therapy were assessed
 Dermatology Life Quality Index (DLQI) questionnaire was completed weekly, Quality of Life-Breast Cancer Patient Version was completed at baseline before and at 5 weeks on radiation therapy, and radiation dermatitis was scored using Radiation Therapy Oncology Group (RTOG) scale
 radiation dermatitis and skin bother (includes ≥ 1 of following discomfort, difficulty, trouble, interruption, and irritation) increased incrementally from baseline to week 5
 comparing week 5 to baseline, radiation therapy associated with significant changes in following aspects of skin-related quality of life worsening of symptoms and feelings
 impairment of daily activities
 less leisure time
 worsened personal relationships
 dissatisfaction with treatment
 skin toxicity did not prevent patients from missing school or work
 worsening skin-related quality of life significantly associated with decline in global quality of life, physical and psychological well-being, and social concerns
 Reference – Eur J Oncol Nurs 2018 Apr;33:22
skin toxicity due to radiation therapy may affect multiple dimensions of quality of life based on semistructured interviews
 20 women with stage 0-III breast cancer receiving radiation therapy 5 times weekly for 5-7 weeks were interviewed in their last week of radiation therapy regarding impact on quality of life
 results of interviews skin changes resulting due to radiation therapy affected multiple dimensions of quality of life causing physical discomfort
 body image disturbance
 emotional distress
 day-to-day functioning impairment
 dissatisfaction with radiation treatment
 individual differences may affect experience of skin toxicity
 Reference – Psychooncology 2011 Mar;20(3):260full-text
Guidelines and Resources
Guidelines
International Guidelines
 Multinational Association for Supportive Care in Cancer (MASCC) Skin Toxicity Study Group guideline on prevention and treatment of acute and late radiation reactions can be found in Support Care Cancer 2013 Oct;21(10):2933.
Canadian Guidelines
 Cancer Care Ontario’s Supportive Care Guidelines Group (SCGG) systematic review and practice guideline on prevention and management of acute skin reactions related to radiation therapy can be found in Support Care Cancer 2006 Aug;14(8):802, commentary can be found in Support Care Cancer 2007 Oct;15(10):1219.
European Guidelines
 Eastern Cooperative Oncology Group (ECOG) consensus guideline on avoiding toxicity from combined BRAF inhibitor and radiation treatment can be found in Int J Radiat Oncol Biol Phys 2016 Jun 1;95(2):632full-text, correction can be found in Int J Radiat Oncol Biol Phys 2016 Oct 1;96(2):486.
Consensus guideline on management of radiation dermatitis and coexisting acne-like rash in patients receiving radiation therapy plus EGFR inhibitors for treatment of squamous cell carcinoma of head and neck can be found in Ann Oncol 2008 Jan;19(1):142full-text.
 Italian inter-society recommendations on radiation protection optimization in interventional radiology can be found in Radiol Med 2018 May;123(5):378.
Review Articles
 Review of radiation dermatitis can be found in J Am Acad Dermatol 2006 Jan;54(1):28.
 Review of management can be found in Am Fam Physician 2010 Aug 15;82(4):381.
Review of prevention and treatment of radiation-induced acute dermatitis in head and neck cancer patients can be found in Future Oncol 2018 Feb;14(3):291.
 Review of ionizing radiation can be found in J Invest Dermatol 2012 Mar;132(3 Pt 2):985.
 Review of prevention and cure can be found in Br J Nurs 2014 Sep 11-24;23(16):S24, S26.
 Review of assessment and management can be found in Br J Nurs 2014 Feb 27-Mar 12;23(4):S28, S30.
 Review of symptom management can be found in Semin Oncol 2014 Dec;41(6):764.
 Review of management of cetuximab-induced radiation dermatitis in squamous cell carcinomas of head and neck can be found in Int J Dermatol 2017 Jun;56(6):602.
 Review of genetic susceptibility can be found in Arch Dermatol Res 2017 Jan;309(1):1.
 Review of topical antioxidant therapy can be found in Int J Palliat Nurs 2015 Sep;21(9):446.
 Review of wound healing after radiation therapy can be found in Radiat Oncol 2012 Sep 24;7:162.
 Case reports of radiation recall dermatitis: In patient with docetaxel-induced radiation recall dermatitis can be found in Strahlenther Onkol 2016 Oct;192(10):730
 In patient with sorafenib-induced radiation recall dermatitis can be found in Strahlenther Onkol 2016 May;192(5):342
 In patient with cisplatin-induced radiation recall dermatitis can be found in Strahlenther Onkol 2016 Oct;192(10):730
 In patient with vemurafenib-induced radiation recall dermatitis can be found in Dermatology 2015;230(1):1
MEDLINE Search
To search MEDLINE for (Radiation Dermatitis) with targeted search (Clinical Queries), click therapy, diagnosis, or prognosis.
Patient Information
 Handout from DermNet NZ
 Information on skin and nail changes during cancer treatment from National Cancer Institute or in Spanish
 Handout on radiation therapy side effects from American Cancer SocietyPDF or in Spanish
References
General References Used
The references listed below are used in this DynaMed topic primarily to support background information and for guidance where evidence summaries are not felt to be necessary. Most references are incorporated within the text along with the evidence summaries.
Hegedus F, Mathew LM, Schwartz RA. Radiation dermatitis: an overview. Int J Dermatol. 2017 Sep;56(9):909-914.
Bray FN, Simmons BJ, Wolfson AH, Nouri K. Acute and Chronic Cutaneous Reactions to Ionizing Radiation Therapy. Dermatol Ther (Heidelb). 2016 Jun;6(2):185-206full-text.
Singh M, Alavi A, Wong R, Akita S. Radiodermatitis: A Review of Our Current Understanding. Am J Clin Dermatol. 2016 Jun;17(3):277-92.
Wong RK, Bensadoun RJ, Boers-Doets CB, et al. Clinical practice guidelines for the prevention and treatment of acute and late radiation reactions from the MASCC Skin Toxicity Study Group. Support Care Cancer. 2013 Oct;21(10):2933-48.
Spałek M. Chronic radiation-induced dermatitis: challenges and solutions. Clin Cosmet Investig Dermatol. 2016;9:473-482full-text.
Recommendation Grading Systems Used
 Multinational Association for Supportive Care in Cancer (MASCC) grading system for recommendations: Levels of evidence: Level I – evidence reserved for meta-analyses of randomized controlled trials or randomized trials with high power
 Level II – evidence includes randomized trials with lower power
 Level III – evidence includes nonrandomized trials, such as cohort or case-controlled series
 Level IV – evidence includes descriptive and case studies
 Level V – evidence includes case reports and clinical examples
 Grades of recommendation: Grade A – level I evidence or consistent findings from multiple studies of level II, III, or IV evidence
 Grade B – level II, III, or IV evidence with generally consistent findings
 Grade C – similar to grade B but with inconsistencies, or where a single lower power study only available
 Grade D – little or no evidence
 Reference – MASCC clinical practice guideline on prevention and treatment of acute and late radiation reactions (Support Care Cancer 2013 Oct;21(10):2933)
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Level 1 (likely reliable) EvidenceLevel 1 indicates research results addressing clinical outcomes and meeting an extensive set of quality criteria which minimizes bias.
There are two types of conclusions which can earn a Level 1 label: levels of evidence for conclusions derived from individual studies and levels of evidence for conclusions regarding a body of evidence.
Level 2 (mid-level) EvidenceLevel 2 indicates research results addressing clinical outcomes, and using some method of scientific investigation, but not meeting the quality criteria to achieve Level 1 evidence labeling.
Level 3 (mid-level) EvidenceLevel 3 indicates evidence that is not based on scientific analysis of clinical outcomes. Examples include case series, case reports, expert opinion, conclusions extrapolated indirectly from scientific studies, and studies that only report surrogate outcomes.

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