Guideline for the Prevention of Oral and Oropharyngeal Mucositis
COG Supportive Care Endorsed Guidelines
Click here to see all the COG Supportive Care Endorsed Guidelines.
DISCLAIMER
For Informational Purposes Only: The information and contents offered in or in connection with the Children’s Oncology
Group Supportive Care Endorsed Guidelines (the “Guidelines”) is provided only for informational purposes to children
affected by cancer, their families and their health care providers. The Guidelines are not intended to substitute for medicaladvice, medical care, diagnosis or treatment obtained from doctors or other healthcare providers.
While the Children’s Oncology Group tries to provide accurate and up-to-date information, the information in theGuidelines may be or may become out of date or incomplete. The information and guidelines may not conform to current
standard of care, state-of-the art, or best practices for a particular disease, condition, or treatment. Some information in theGuidelines may be intended to be used by clinical researchers in special clinical settings or situations that may not apply toyou, your child or your patient.
Special Notice to cancer patients and their parents and legal guardians: The Children’s Oncology Group is a researchorganization and does not provide individualized medical care or treatment.
The Guidelines are not intended to replace the independent clinical judgment, medical advice, screening, health counseling,or other intervention performed by your or your child’s doctor or other healthcare provider. Please do not rely on thisinformation exclusively and seek the care of a doctor or other medical professional if you have any questions regarding theGuidelines or a specific medical condition, disease, diagnosis or symptom.
Please contact “911” or your emergency services for any health emergency!
Special Notice to physicians and other healthcare providers: This document is aimed specifically at members of theChildren’s Oncology Group or Member affiliates who have agreed to collaborate with the Children’s Oncology Group inaccordance with the relevant procedures and policies for study conduct and membership participation. Requirements andrestrictions applicable to recipients of U.S. governmental funds or restrictions governing certain private donations may applyto the use and distribution of the Guidelines and the information contained herein.
The Guidelines are not intended to replace your independent clinical judgment, medical advice, or to exclude other legitimate
criteria for screening, health counseling, or intervention for specific complications of childhood cancer treatment. TheGuidelines provided are not intended as a sole source of guidance in the evaluation of childhood cancer patients. Nor are
the Guidelines intended to exclude other reasonable alternative care. Specific patient care decisions are the prerogative of
the patient, family and healthcare provider.
Warranty or Liability Assumed by Children’s Oncology Group and Related Parties: While the Children's Oncology
Group has tried to assure that the Guidelines are accurate and complete as of the date of publication, no warranty orrepresentation, express or implied, is intended to be made in or with the Guidelines. No liability is assumed by the Children's
Oncology Group or any affiliated party or member thereof for damage resulting from the use, review, or access of theGuidelines.

1

The “Clinical practice guideline for the prevention of oral and oropharyngeal mucositis in pediatriccancer and hematopoietic stem cell transplant patients: 2021 update” developed by the PediatricOncology Group of Ontario (POGO) was endorsed by the COG Supportive Care Guideline Committee inDecember 2021.
The source clinical practice guideline is published (Patel P, et al. Clinical practice guideline for theprevention of oral and oropharyngeal mucositis in pediatric cancer and hematopoietic stem celltransplant patients: 2021 update. Eur J Cancer 2021; 154: 92-101.) and is available
at: https://www.sciencedirect.com/science/article/pii/S095980492100321X
The purpose of the source clinical practice guideline was to update the 2015 clinical practice guidelinefor mucositis prevention in pediatric cancer and HSCT patients. The recommendations of the source
clinical practice guideline are presented below.

Summary of Recommendations for the Prevention of Oral and Oropharyngeal Mucositis
Strength ofRecommendation
andQuality of Evidence*
What prophylactic interventions are effective at preventing or reducing the severity of oral andoropharyngeal mucositis in pediatric patients (0 to 18 years) receiving treatment for cancer orundergoing HSCT?
1. Use cryotherapy for older, cooperative pediatric patients receiving
Strong recommendation
treatment for cancer or undergoing HSCT who will receive short
High-quality evidence
infusions of melphalan or 5-fluorouracil.
RECOMMENDATIONS

Remarks: The panel valued the absence of documented adverse
effects, low costs and consistent benefits associated withcryotherapy. The duration of melphalan and 5-fluorouracil
administration in the included trials was 30 min or less whereinfusion duration was described. The panel did not believe thatcryotherapy would be feasible for chemotherapy administrations
longer than 1 h.

2Version date: February 7, 2022

RECOMMENDATIONS
2. Consider using cryotherapy for older, cooperative pediatricpatients receiving treatment for cancer or undergoing HSCT who will
receive short infusions of chemotherapy associated with mucositis
other than melphalan or 5-fluorouracil.
Remarks: The panel hypothesized that the efficacy of cryotherapy islikely generalizable to chemotherapy other than melphalan and 5fluorouracil. However, the indirectness of the data lowered thepanel's certainty and resulted in a conditional recommendation. It is
important to counsel families and patients that mucositis may
develop even with diligent cryotherapy use, and the efficacy ofcryotherapy may vary depending on the chemotherapy regimenadministered.
3. Do not administer palifermin routinely to pediatric patients withcancer receiving treatment for cancer or undergoing HSCT.
Remarks: While the panel acknowledged the significant reduction insevere mucositis associated with palifermin, the observed effect size
was relatively modest. Based on its known short-term adverse
effects, its potential for long-term negative effects on cancer
outcomes, high costs and restricted availability, the panel made astrong recommendation against its routine use.
4. Use intraoral photobiomodulation therapy in the red light
spectrum (620–750 nm) for pediatric patients undergoing autologous
or allogeneic HSCT and for pediatric patients who will receive
radiotherapy for head and neck carcinoma.
Remarks: The panel valued the consistent benefits ofphotobiomodulation therapy and data regarding feasibility inpediatric patients. The ability to deliver photobiomodulation therapy
requires specialized equipment, training and protective eyewear forthe patient and those in attendance. The panel believed theserequirements to be acceptable given the magnitude of benefit andthe restricted patient populations included in the recommendation
based on direct data. The ability to deliver photobiomodulation
therapy to very young children requires assistance and support fromfamily members and may not always be successful.

3Version date: February 7, 2022

Strength ofRecommendation
andQuality of Evidence*
Conditional recommendation
Moderate-quality evidence

Strong recommendation
High-quality evidence

Strong recommendation
High-quality evidenceRECOMMENDATIONS
5. Consider using intraoral photobiomodulation therapy in the red
light spectrum (620–750 nm) for pediatric patients who will receive
radiotherapy for head and neck cancers other than carcinoma.
Remarks: Although direct data were not available, the panel
hypothesized that the efficacy of photobiomodulation therapy forhead and neck carcinoma patients receiving radiotherapy is likely
generalizable to pediatric patients who will receive radiotherapy forother head and neck cancers such as rhabdomyosarcoma. However,
the indirectness of the data lowered the panel's certainty andresulted in a conditional recommendation.
6. Do not administer GCSFs to pediatric patients receiving treatment
for cancer or undergoing HSCT for the purpose of mucositis
prevention.

Strength ofRecommendation
andQuality of Evidence*
Conditional recommendation
Moderate-quality evidence

Strong recommendation
High-quality evidence

Remarks: While the panel recognized that patients receive GCSFs forother indications including shortening the duration of neutropenia,
the absence of benefit, adverse effects and costs led the panel tomake a strong recommendation against its use for the purpose ofmucositis prevention.
*see Appendix 1
HSCT: hematopoietic stem cell transplant; GCSFs: granulocyte colony-stimulating factors

4
Version date: February 7, 2022

Appendix 1: GRADE
Strength of Recommendations:
StrongRecommendation

When using GRADE, panels make strong recommendations when they are confident
that the desirable effects of adherence to a recommendation outweigh theundesirable effects.

Weak orConditionalRecommendation

Weak or conditional recommendations indicate that the desirable effects of adherence to a recommendation probably outweigh the undesirable effects, but the panelis less confident.

Strength of Recommendation Determinants:
FactorBalance between desirable andundesirable effects

Certainty in evidence
Values and preferences

Costs (resource allocation)

Comment
The larger the difference between the desirable and undesirable
effects, the higher the likelihood that a strong recommendation iswarranted. The narrower the gradient, the higher the likelihood that aweak recommendation is warranted
The higher the quality of evidence, the higher the likelihood that astrong recommendation is warranted
The more values and preferences vary, or the greater the uncertaintyin values and preferences, the higher the likelihood that a weakrecommendation is warranted
The higher the costs of an intervention—that is, the greater theresources consumed—the lower the likelihood that a strong
recommendation is warranted

Certainty in Evidence or Quality of EvidenceHigh
Certainty/Quality

Further research is very unlikely to change our confidence in the estimate of effectModerate
Certainty/Quality

Further research is likely to have an important impact on our confidence in theestimate of effect and may change the estimate

Low
Certainty/Quality

Further research is very likely to have an important impact on our confidence in theestimate of effect and is likely to change the estimate

Very Low
Certainty/Quality

Any estimate of effect is very uncertain

Guyatt, G.H., et al., GRADE: an emerging consensus on rating quality of evidence and strength ofrecommendations. BMJ, 2008; 336: 924-926.
Guyatt, G.H., et al., GRADE: going from evidence to recommendations. BMJ, 2008; 336: 1049-1051.

5Version date: February 7, 2022