VOLUME 35 • NUMBER 36 • DECEMBER 20, 2017

JOURNAL OF CLINICAL ONCOLOGY A S C O S P E C I A L A R T I C L E

Radiation Therapy for Oropharyngeal Squamous Cell

Carcinoma: American Society of Clinical Oncology
Endorsement of the American Society for Radiation
Oncology Evidence-Based Clinical Practice Guideline
Harry Quon, Neha Vapiwala, Arlene Forastiere, Erin B. Kennedy, David J. Adelstein, Holly Boykin, Joseph A.
Califano, F. Chris Holsinger, Brian Nussenbaum, David I. Rosenthal, Lillian L. Siu, and John N. Waldron

Author affiliations and support information

(if applicable) appear at the end of this
article.
Published at jco.org on October 24, 2017.
H.Q., N.V., and A.F. were Endorsement
Panel co-chairs.
Clinical Practice Guideline Committee
approved: February 27, 2017.
Editor’s note: This American Society of
Clinical Oncology Clinical Practice
Guideline provides recommendations,
with comprehensive review and analyses
of the relevant literature for each
recommendation. Additional information,
including a Data Supplement, a
Methodology Supplement, slide sets,
clinical tools and resources, and links to
patient information at www.cancer.net,
is available at www.asco.org/head-neck-
cancer-guidelines and www.asco.org/
guidelineswiki.
Reprint requests: American Society of
Clinical Oncology, 2318 Mill Rd, Ste 800,
Alexandria, VA 22314; guidelines@
asco.org.
Corresponding author: American Society
of Clinical Oncology, 2318 Mill Rd, Ste
800, Alexandria, VA 22314; e-mail:
guidelines@asco.org.
© 2017 by American Society of Clinical
Oncology
0732-183X/17/3536w-4078w/$20.00
A B S T R A C T
Purpose
The American Society for Radiation Oncology (ASTRO) produced an evidence-based guideline
on radiation therapy in oropharyngeal squamous cell carcinoma (OPSCC) that was determined to
be relevant to the American Society of Clinical Oncology (ASCO) membership. After applying
standard critical appraisal policy and endorsement procedures, ASCO chose to endorse the
ASTRO guideline.
Methods
The ASTRO guideline was reviewed by ASCO content experts for clinical accuracy and by ASCO
methodologists for developmental rigor. On favorable review, an ASCO Expert Panel was convened
to review the guideline contents and recommendations. The ASCO guideline approval body, the
Clinical Practice Guidelines Committee, approved the final endorsement.
Results
The ASCO Expert Panel determined that the ASTRO guideline recommendations, published in July
2017, are clear, thorough, and based upon the most relevant scientific evidence. ASCO endorsed
the ASTRO guideline and added minor qualifying statements.
Recommendations
Recommendations for the addition of systemic therapy to definitive radiotherapy in the treatment of
OPSCC, postoperative radiotherapy with and without systemic therapy following primary surgery of
OPSCC, induction chemotherapy in the treatment of OPSCC, and the appropriate dose, fraction-
ation, and volume regimens with and without systemic therapy in the treatment of OPSCC are
outlined for a variety of disease stages and clinical scenarios. ASCO Endorsement Panel qualifying
statements and minor modifications were made to the ASTRO recommendations. The staging
system that is referenced in these guidelines is the American Joint Committee on Cancer Staging
Manual, 7th edition. Additional information is available at: www.asco.org/head-neck-cancer-
guidelines and www.asco.org/guidelineswiki.

J Clin Oncol 35:4078-4090. © 2017 by American Society of Clinical Oncology

human papillomavirus (HPV)–associated cancers

INTRODUCTION
Oropharyngeal squamous cell carcinoma (OPSCC)
ASSOCIATED CONTENT
includes cancers of the tonsils, base of the tongue,
Appendix soft palate, and upper lateral and posterior pha-
DOI: https://doi.org/10.1200/JCO.
2017.73.8633
ryngeal walls. In 2016, an estimated 48,330 new
cases of cancer of the oral cavity and pharynx were
Data Supplement
DOI: https://doi.org/10.1200/JCO.
expected to be diagnosed in the United States.1
2017.73.8633 Incidence rates are more than twice as high in men
DOI: https://doi.org/10.1200/JCO.2017. compared with women.2 Over the past few decades,
73.8633 a shift has occurred such that the incidence of
of the oropharynx has increased, while the in-
cidence of HPV-negative tobacco-driven OPSCC
has declined. Patients with HPV-positive OPSCC
tend to be more frequently male, younger, and
have a better performance status and prognosis.
The options for curative management of OPSCC
include surgery with or without adjuvant radio-
therapy (with concurrent chemotherapy in selected
cases) and primary radiotherapy with or without
concurrent systemic therapy. To provide guidance
on the use of definitive or adjuvant radiation

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 Radiation Therapy for Oropharyngeal Squamous Cell Carcinoma Guideline

THE BOTTOM LINE

Radiation Therapy for Oropharyngeal Squamous Cell Carcinoma: American Society of Clinical Oncology
Endorsement of the American Society for Radiation Oncology Evidence-Based Clinical Practice Guideline

Guideline Question
What is the role of definitive or adjuvant radiation therapy in the treatment of oropharyngeal squamous cell carcinoma (OPSCC)?

Target Population
Adults with any stage of OPSCC.

Target Audience
Medical, radiation, and surgical oncology clinicians, including head and neck and oral surgeons, and other providers.

Methods
An ASCO Expert Panel was convened to consider endorsing the ASTRO Radiotherapy for Oropharyngeal Squamous Cell Carcinoma
Evidence-Based Guideline recommendations that were based on a systematic review of the medical literature. The ASCO Expert Panel
considered the methodology used in the ASTRO guideline by considering the results from the AGREE II review instrument. The ASCO
Expert Panel carefully reviewed the ASTRO guideline content to determine appropriateness for ASCO endorsement.

Recommendations
ASTRO recommendations are listed here, with qualifying statements or modifications added by the ASCO panel listed in bold italics.

ASCO Qualifying Statement: For this version of the guideline, recommendations for radiation therapy for OPSCC do not vary by
human papillomavirus (HPV) status. Clinical trials are ongoing to assess the need for risk stratification in the treatment of OPSCC
by HPV status. As such, these guidelines, though currently accurate, will likely need to be updated when such evidence becomes
available in the future. In addition, the staging system that is referenced in these guidelines is the American Joint Committee on
Cancer (AJCC) Staging Manual, 7th edition. With the implementation of the AJCC Manual, 8th edition, which is expected to begin
on January 1, 2018, there will be important changes, such as stage migration due to reclassification of selected scenarios and the
divergence of OPSCC into two distinct prognostic groups based on HPV status. At that transition, these guidelines must be
interpreted in the context of the two different staging systems.

1. Recommendations for the addition of systemic therapy to definitive radiotherapy in the treatment of OPSCC.
In the scenario of AJCC stage IVA-IVB disease:
• Concurrent high-dose intermittent cisplatin should be delivered to patients with stage IVA-IVB OPSCC receiving
definitive radiotherapy (Recommendation strength: strong; Quality of evidence: high).

• Concurrent cetuximab or carboplatin-fluorouracil may be delivered to patients with stage IVA-IVB OPSCC receiving
definitive radiotherapy who are not medically fit for high-dose cisplatin (Recommendation strength: conditional; Quality
of evidence: high).
• Concurrent weekly cisplatin may be delivered to patients with stage IVA-IVB OPSCC receiving definitive radiotherapy
who are not medically fit for high-dose cisplatin, after a careful discussion of patient preferences and the limited
prospective data supporting this regimen (Recommendation strength: conditional; Quality of evidence: low).
• Concurrent cetuximab should not be delivered in combination with chemotherapy to patients with stage IVA-IVB OPSCC
receiving definitive radiotherapy (Recommendation strength: strong; Quality of evidence: high).

• Intra-arterial chemotherapy should not be delivered to patients with stage IVA-IVB OPSCC receiving definitive
radiotherapy (Recommendation strength: strong, Quality of evidence: high).
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 Quon et al

THE BOTTOM LINE (CONTINUED)

In the scenario of stage III disease:
• Concurrent systemic therapy should be delivered to patients with T3 N0-1 OPSCC receiving definitive radiotherapy
(Recommendation strength: strong, Quality of evidence: moderate).

• Concurrent systemic therapy may be delivered to patients with T1-T2 N1 OPSCC receiving definitive radiotherapy who
are considered at particularly significant risk for locoregional recurrence, after a careful discussion of patient preferences
and the limited evidence supporting its use (Recommendation strength: conditional, Quality of evidence: low).
In the scenario of stage I-II disease:
• Concurrent systemic therapy should not be delivered to patients with stage I-II OPSCC receiving definitive radiotherapy
(Recommendation strength: strong, Quality of evidence: low).
2. Recommendations for delivery of postoperative radiotherapy with and without systemic therapy following primary surgery of
OPSCC.
In the scenario of positive margins and/or extracapsular nodal extension:
• Concurrent high-dose intermittent cisplatin should be delivered with postoperative radiotherapy to patients with positive
surgical margins and/or extracapsular nodal extension; this high-risk population includes patients independent of HPV
status or the extent of extranodal tumor (Recommendation strength: strong, Quality of evidence: moderate).

• Concurrent weekly cisplatin may be delivered with postoperative radiotherapy to patients who are considered
inappropriate for standard high-dose intermittent cisplatin after a careful discussion of patient preferences and the limited
evidence supporting this treatment schedule (Recommendation strength: conditional, Quality of evidence: low).

• For the high-risk postoperative patient unable to receive cisplatin-based concurrent chemoradiotherapy, radiotherapy
alone should be routinely delivered without concurrent systemic therapy; given the limited evidence supporting
alternative regimens, treatment with noncisplatin systemic therapy should be accompanied by a careful discussion of the
risks and unknown benefits of the combination (Recommendation strength: strong, Quality of evidence: moderate).
• Patients treated with postoperative radiotherapy should not receive concurrent weekly carboplatin (Recommendation
strength: strong, Quality of evidence: moderate).
• Patients treated with postoperative radiotherapy should not receive cetuximab, either alone or in combination with
chemotherapy, although such regimens are currently under investigation (Recommendation strength: strong, Quality of
evidence: low).

• Patients treated with postoperative radiotherapy should not routinely receive concurrent weekly docetaxel given the
limited evidence supporting its use, although such regimens are currently under investigation (Recommendation strength:
strong, Quality of evidence: low).

• Patients treated with postoperative radiotherapy should not receive concurrent mitomycin-C, alone or with bleomycin, given
the limited evidence and experience supporting its use (Recommendation strength: strong, Quality of evidence: moderate).
• Postoperative chemotherapy should not be delivered alone or sequentially with postoperative radiotherapy
(Recommendation strength: strong, Quality of evidence: high).
In the scenario of intermediate-risk pathologic factors such as lymphovascular invasion (LVI), perineural invasion (PNI), T3-T4
disease, or positive lymph nodes:
• Patients with intermediate-risk factors should not routinely receive concurrent systemic therapy with postoperative
radiotherapy (Recommendation strength: strong, Quality of evidence: moderate).

• Patients with intermediate-risk factors whose surgical procedure and/or pathologic findings imply a particularly
significant risk of locoregional recurrence may receive concurrent cisplatin-based chemotherapy after a careful
discussion of patient preferences and the limited evidence supporting its use in this scenario; alternative systemic
treatment regimens should only be used in the context of a clinical trial (Recommendation strength: conditional,
Quality of evidence: low).
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 Radiation Therapy for Oropharyngeal Squamous Cell Carcinoma Guideline

THE BOTTOM LINE (CONTINUED)

• Postoperative radiotherapy should be delivered to patients with pathologic T3 or T4 disease (Recommendation strength:
strong, Quality of evidence: low).

• Postoperative radiotherapy should be delivered to patients with pathologic N2 or N3 disease (Recommendation strength:
strong, Quality of evidence: low).
• Postoperative radiotherapy may be delivered to patients with pathologic N1 disease without extracapsular nodal
extension after a careful discussion of patient preferences and the limited evidence of outcomes following surgery alone in
this scenario (Recommendation strength: conditional, Quality of evidence: low).
• Postoperative radiotherapy may be delivered to patients with LVI and/or PNI as the only risk factor(s) after a careful
discussion of patient preferences and the limited evidence of outcomes following surgery alone in this scenario
(Recommendation strength: conditional Quality of evidence: low).
In the scenario of no pathologic risk factors:
• Postoperative radiotherapy may be delivered to patients without conventional adverse pathologic risk factors only if the
clinical and surgical findings imply a particularly significant risk of locoregional recurrence, after a careful discussion of
patient preferences and the potential harms and benefits of radiotherapy (Recommendation strength: conditional, Quality
of evidence: low).
3. Recommendations for the use of induction chemotherapy in the treatment OPSCC.
• Induction chemotherapy should not be routinely delivered to patients with OPSCC (Recommendation strength: strong,
Quality of evidence: high).
4. Recommendations for the appropriate dose, fractionation, and volume regimens with and without systemic therapy in the treatment
of OPSCC.
In the scenario of definitive nonsurgical therapy:
• A dose of 70 Gy over 7 weeks should be delivered to gross primary and nodal disease in patients with stage III-IV OPSCC
selected to receive standard, once-daily definitive radiotherapy (Recommendation strength: strong, Quality of evidence:
moderate).
• The biologically equivalent dose of approximately 50 Gy in 2-Gy fractions or slightly higher should be delivered electively
to clinically and radiographically negative regions at risk for microscopic spread of tumor (Recommendation strength:
strong, Quality of evidence: low).
• Altered fractionation should be used in patients with stage IVA-IVB OPSCC treated with definitive radiotherapy who are
not receiving concurrent systemic therapy (Recommendation strength: strong, Quality of evidence: high).

• Either accelerated radiotherapy or hyperfractionated radiotherapy may be used in patients with OPSCC treated with
altered fractionation definitive radiotherapy after a careful discussion of patient preferences and the limited evidence
supporting one regimen over the other (Recommendation strength: conditional, Quality of evidence: high).

• Either standard, once-daily radiotherapy or accelerated fractionation may be used when treating OPSCC with concurrent
systemic therapy after a careful discussion of patient preferences and the risks and benefits of both approaches
(Recommendation strength: conditional, Quality of evidence: high).
ASCO qualifying statement: In the Danish Head and Neck Cancer Group randomized controlled trial of 1,485 patients with
squamous cell carcinoma of the head and neck (larynx, pharynx, and oral cavity), standard radiotherapy was defined as 66 to
68 Gy, delivered in 2-Gy fractions, five fractions per week, compared with the accelerated arm, which received the same dose at
a rate of six fractions per week, resulting in the same dose delivered over 7 or 6 weeks, respectively.4

• Altered fractionation should be used in patients with T3 N0-1 OPSCC treated with definitive radiotherapy who do not
receive concurrent systemic therapy (Recommendation strength: strong, Quality of evidence: moderate).
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 Quon et al

THE BOTTOM LINE (CONTINUED)

• Altered fractionation may be used in patients with T1-2 N1 or T2 N0 OPSCC treated with definitive radiotherapy alone who are
considered at particularly significant risk of locoregional recurrence, after a careful discussion of patient preferences and the limited
evidence supporting its use in this scenario (Recommendation strength: conditional, Quality of evidence: low).
In the scenario of adjuvant postoperative radiotherapy:
• Adjuvant postoperative radiotherapy should be delivered to regions of microscopically positive primary site surgical
margins and extracapsular nodal extension at 2 Gy/fraction once daily to a total dose between 60 and 66 Gy
(Recommendation strength: strong, Quality of evidence: moderate).

• Adjuvant postoperative radiotherapy delivered without concurrent systemic therapy should treat regions of
microscopically positive primary site surgical margins and extracapsular nodal extension at 2 Gy/fraction once daily to
a total dose of 60 to 66 Gy, although there are limited data guiding this recommendation (Recommendation strength:
conditional, Quality of evidence: weak).

ASCO qualifying statement: In the setting of single-modality postoperative radiotherapy, the time from surgery to the completion of
radiotherapy should be kept as short as possible, ideally < 85 day, as the time to completion of postoperative radiotherapy may be the
most important radiotherapy factor and not the dose per se.5

• Adjuvant postoperative radiotherapy should be delivered to the tumor bed and involved, dissected lymph node regions at
once-daily fractionation to a total dose of 56 to 60 Gy in the absence of primary site positive margins and extracapsular
nodal extension (Recommendation strength: strong, Quality of evidence: moderate).
In the scenario of early T-stage tonsillar carcinoma:
• Unilateral radiotherapy should be delivered to patients with well-lateralized (no soft palate extension or base of tongue
involvement), T1-T2 tonsillar cancer, and N0-N1 nodal category (Recommendation strength: strong, Quality of evidence:
moderate).

• Unilateral radiotherapy may be delivered to patients with lateralized (, 1 cm of soft palate extension but without base of tongue
involvement) T1-T2 N0-N2b tonsillar cancer without clinical or radiographic evidence of extracapsular extension, after careful
discussion of patient preferences and the relative benefits of unilateral treatment versus the potential for contralateral nodal
recurrence and subsequent salvage treatment (Recommendation strength: conditional, Quality of evidence: low).

Additional Resources
More information, including a Methodology Supplement, is available at www.asco.org/head-neck-cancer-guidelines and www.asco.
org/guidelineswiki. Patient information is available at www.cancer.net.
Full text of “Radiation Therapy for Oropharyngeal Squamous Cell Carcinoma: An American Society for Radiation Oncology (ASTRO)
Evidence-Based Clinical Practice Guideline” is available at http://www.practicalradonc.org/article/S1879-8500(17)30045-0/. This
publication includes further information about the strength of each recommendation and the quality of the evidence.

ASCO believes that cancer clinical trials are vital to inform medical decisions and improve cancer care, and that all patients should
have the opportunity to participate.

Recommendations reprinted from Sher et al, 2017,3 with permission.

therapy for OPSCC, the American Society for Radiation On-
cology published evidence-based recommendations in Practical
Radiation Oncology in July 2017. At this time, the evidence base
is not sufficiently developed to allow different recommendations
for radiation therapy for OPSCC according to HPV status;
however, with continued accrual to clinical trials, it may be
possible to make more specific recommendations in the future.3
The purpose of this American Society of Clinical Oncology
(ASCO) guideline is to critically appraise and endorse the ASTRO
guideline on radiation therapy for OPSCC. This endorsement
reinforces the recommendations provided in the ASTRO guide-
line and acknowledges the effort put forth by ASTRO to produce
an evidence-based guideline informing practitioners who care
for patients with OPSCC. The ASTRO recommendations are
listed in the Bottom Line Box, with qualifying statements from
the ASCO Endorsement Panel. The full ASTRO guideline is
available at: http://www.practicalradonc.org/article/S1879-8500
(17)30045-0/.

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 Radiation Therapy for Oropharyngeal Squamous Cell Carcinoma Guideline
OVERVIEW OF THE ASCO GUIDELINE ENDORSEMENT PROCESS
ASCO has policies and procedures for endorsing practice guide-
lines that have been developed by other professional organizations.
The goal of guideline endorsement is to increase the number of
high-quality, ASCO-vetted guidelines available to the ASCO mem-
bership. The ASCO endorsement process involves an assessment
by ASCO staff of candidate guidelines for methodological quality
using the Rigour of Development subscale of the Appraisal of
Guidelines for Research and Evaluation II (AGREE II) instru-
ment. (See Methodology Supplement for more detail.)
Disclaimer
The clinical practice guidelines and other guidance published
herein are provided by the American Society of Clinical On-
cology, Inc. (“ASCO”) to assist providers in clinical decision
making. The information therein should not be relied upon as
being complete or accurate, nor should it be considered as in-
clusive of all proper treatments or methods of care or as
a statement of the standard of care. With the rapid development
of scientific knowledge, new evidence may emerge between the
time information is developed and when it is published or read.
The information is not continually updated and may not reflect
the most recent evidence. The information addresses only the
topics specifically identified therein and is not applicable to other
interventions, diseases, or stages of diseases. This information
does not mandate any particular course of medical care. Further,
the information is not intended to substitute for the independent
professional judgment of the treating provider, as the information
does not account for individual variation among patients. Rec-
ommendations reflect high, moderate, or low confidence that the
recommendation reflects the net effect of a given course of action.
The use of words like “must,” “must not,” “should,” and “should
not” indicate that a course of action is recommended or not
recommended for either most or many patients, but there is
latitude for the treating physician to select other courses of action
in individual cases. In all cases, the selected course of action
should be considered by the treating provider in the context of
treating the individual patient. Use of the information is vol-
untary. ASCO provides this information on an “as is” basis, and
makes no warranty, express or implied, regarding the in-
formation. ASCO specifically disclaims any warranties of mer-
chantability or fitness for a particular use or purpose. ASCO
assumes no responsibility for any injury or damage to persons or
property arising out of or related to any use of this information or
for any errors or omissions.
Guideline and Conflicts of Interest
The Expert Panel was assembled in accordance with ASCO’s
Conflict of Interest Policy Implementation for Clinical Practice
Guidelines (“Policy,” found at http://www.asco.org/rwc). All
members of the Expert Panel completed ASCO’s disclosure form,
which requires disclosure of financial and other interests, in-
cluding relationships with commercial entities that are reasonably
likely to experience direct regulatory or commercial impact as a
result of promulgation of the guideline. Categories for disclosure
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include employment; leadership; stock or other ownership; hono-
raria, consulting or advisory role; speaker’s bureau; research funding;
patents, royalties, other intellectual property; expert testimony;
travel, accommodations, expenses; and other relationships. In
accordance with the Policy, the majority of the members of the
Expert Panel did not disclose any relationships constituting a conflict
under the Policy.
ASTRO CLINICAL QUESTIONS AND TARGET POPULATION
The ASTRO guideline addressed four key clinical questions
regarding the treatment of OPSCC: (1) When is it appropriate
to add systemic therapy to definitive radiotherapy in (a) stage
IVA-IVB disease, (b) stage III disease, or (c) stage I-II disease?
(2) When is it appropriate to deliver postoperative radiotherapy
with and without systemic therapy following primary surgery in
the scenario of (a) positive margins and/or extracapsular nodal
extension; (b) intermediate-risk pathologic factors such as lym-
phovascular invasion, perineural invasion, T3-4 disease, or pos-
itive lymph nodes; or (c) no pathologic risk factors? (3) When is it
appropriate to use induction chemotherapy? (4) What is the
appropriate dose, fractionation, and volume regimen with and
without systemic therapy in the treatment of OPSCC in (a) the
scenario of definitive nonsurgical therapy; (b) the scenario of
postoperative radiotherapy; and (c) the scenario of early T-stage
tonsillar carcinoma? The target population for the ASTRO guideline
is patients with any stage of OPSCC. Systemic therapy in the absence
of radiotherapy was outside the scope of the ASTRO guideline
development process and the ASCO endorsement process.
SUMMARY OF THE ASTRO GUIDELINE DEVELOPMENT AND ASCO
ENDORSEMENT METHODOLOGY
ASTRO identified OPSCC as a disease that provides many challenges
to the radiation oncologist and other members of the multidisci-
plinary team, and given its increasing prevalence and variety of
treatment options, ASTRO determined that OPSCC was a high-
priority topic in need of an evidence-based practice guideline.
The guideline was developed under the auspices of the Guidelines
Subcommittee of the Clinical Affairs and Quality Committee of
ASTRO, which formed the Oropharyngeal Squamous Cell Car-
cinoma Guideline panel that included experts in oropharyngeal
cancer, including radiation oncologists, medical oncologists,
otolaryngologists, and a patient advocate. The panel was co-chaired
by Avraham Eisbruch, MD, and David J. Sher, MD, MPH. In
September 2014, the ASTRO Board of Directors approved the
proposed research questions and panel membership. A draft
of the manuscript was also reviewed by three expert external
reviewers.
A systematic review was completed for each of the four key
questions. The searches were conducted in PubMed MEDLINE
for studies fully published between 1990 and December 2014.
Randomized controlled trials (RCTs) and nonrandomized studies
were eligible for inclusion. Details of the search strategies and
the study inclusion criteria and outcomes of interest are available
© 2017 by American Society of Clinical Oncology 4083
 Quon et al
at the ASTRO guideline URL, http://www.practicalradonc.org/
article/S1879-8500(17)30045-0/, and the ASTRO search terms
are provided in the Data Supplement. The searches identified
119 studies for inclusion that were abstracted into detailed
literature tables to provide supporting evidence for the clinical
guideline recommendations.
The members of the task force were divided into four writing
groups by key questions, according to their areas of expertise. They
completed the systematic reviews, created evidence tables, evalu-
ated the evidence quality, and drafted the guideline. Evidence
was graded and recommendation strength determined using the
Grades of Recommendation, Assessment, Development and
Evaluation (GRADE) methodology. A predefined modified Delphi
process was implemented to survey the panel membership and
arrive at the final recommendation statements. Where this process
resulted in a “Strong” recommendation with “Low” quality of
evidence, or a “Conditional” strength recommendation based on
“High” quality evidence, it is a reflection of the contribution of
expert opinion to the recommendations development process.
Detailed review of key evidence and the interpretation of evidence
that supports the strength of recommendations can be found in the
ASTRO guideline.3 The initial draft of the ASTRO manuscript was
reviewed by the three expert reviewers and ASTRO legal counsel. A
revised draft was placed on the ASTRO Web site in April 2016 for
a 6-week period of public comment. Following integration of the
feedback, the document was submitted for approval to the ASTRO
Board of Directors in October 2016. The ASTRO Expert Panel
completed their final revisions prior to the commencement of the
ASCO endorsement process; therefore, the ASTRO panel did not
re-review the ASCO qualifying statements and modifications.
The ASCO endorsement was developed by an author Expert
Panel that included individuals who were selected for their ex-
pertise in medical oncology, radiation oncology, surgical oncology,
patient advocacy, and guideline implementation, as well as consid-
eration of geographic diversity. Further details related to the ASCO
endorsement process, including results of the methodology review,
content review, and updated literature review, are included below.
RESULTS OF THE ASCO METHODOLOGY REVIEW
The methodology review of the ASTRO guideline was completed
independently by two ASCO guideline staff members using the
Rigor of Development subscale from the AGREE II instrument.
The two reviewers rated the guideline highly on rigor of devel-
opment with an overall score of 88% (Methodology Supplement).
The preliminary ASCO content reviewers of the ASTRO guideline,
as well as the ASCO Expert Panel, found the recommendations well
supported in the original guideline. Each section, including an
introduction, methods and materials, results, conclusion, clinical
questions, guideline statement, narrative, and summary tables for
each of the four key questions, was clear and well referenced from
the systematic review. A section of reflections from the patient
advocate provided context for the recommendations.
This is the most recent information as of the publication date.
For updates and the most recent information, and to submit new
evidence, please visit www.asco.org/head-neck-cancer-guidelines
and the ASCO Guidelines Wiki (www.asco.org/guidelineswiki).
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RESULTS OF THE ASCO CONTENT REVIEW
The ASCO Expert Panel reviewed the Radiotherapy for Oro-
pharyngeal Squamous Cell Carcinoma: An American Society for
Radiation Oncology (ASTRO) Evidence-Based Clinical Practice
Guideline and concurs that the recommendations are clear, thor-
ough, based on the most relevant scientific evidence in this content
area, and present options that will be acceptable to patients. Overall,
the ASCO Expert Panel agrees with the recommendations as stated
in the guideline, with the minor qualifications discussed.
METHODS AND RESULTS OF THE ASCO UPDATED
LITERATURE REVIEW
ASCO guidelines staff updated the ASTRO literature search.
MEDLINE was searched from ASTRO’s final search date of January
2014 to July 2016. The search was restricted to articles published
in English and to systematic reviews, meta-analyses, and RCTs.
The updated search for all questions yielded 304 records, of which
four met the inclusion criteria. The results of these studies, which
are outlined briefly, were consistent with the ASTRO guideline
recommendations.
Meta-Analyses
Two meta-analyses of RCTs of induction chemotherapy added
to concurrent chemoradiotherapy (CRT) were found.6,7 The first
of these compared concurrent CRT alone with induction che-
motherapy using docetaxel, cisplatin, and fluorouracil (TPF),
followed by CRT in a subgroup analysis of 314 oropharyngeal
patients from two studies, and found nonsignificant differences in
the hazard ratio (HR) for overall survival (OS; 0.89; 95% CI, 0.62
to 1.28; P = .527) and progression-free survival (0.89; 95% CI,
0.64 to 1.24; P = .504).7 The other meta-analysis of 5 studies, in
which 51.3% of patients had oropharyngeal cancer, found that
induction chemotherapy with TPF followed by concurrent CRT
resulted in nonsignificant differences in OS (HR, 1.010; 95% CI,
0.84 to 1.21; P = .92) and progression-free survival (HR, 0.91;
95% CI, 0.75 to 1.1; P = .32), compared with concurrent CRT
alone.6 Consistent with ASTRO’s recommendation, the authors
conclude that induction chemotherapy with TPF before con-
current CRT does not improve OS for patients with locally ad-
vanced head and neck squamous cell carcinoma. Limitations to
the studies included in the analyses were low patient numbers due
to slow accrual and high rates of noncompletion of scheduled
treatments.
Longer-Term Results From RCTs
New longer-term results for two studies that were included in
the ASTRO review were also found.8,9 An update of the ARO 95-06
trial found that hyperfractionated accelerated chemoradiation with
mitomycin C/fluorouracil remained superior to hyperfractionated
accelerated radiation therapy alone in terms of locoregional control
(P = .03 in patients with oropharyngeal cancer) after a median
follow-up of 8.7 years (95% CI, 7.8 to 9.7 years).8
Longer-term results of the ARTSCAN trial, where patients
were randomly assigned between accelerated fractionation (1.1 Gy
JOURNAL OF CLINICAL ONCOLOGY
 Radiation Therapy for Oropharyngeal Squamous Cell Carcinoma Guideline

Table 1. Original ASTRO and ASCO Endorsement Research Questions, Recommendations, and Qualifying Statements
ASCO Endorsement Recommendation (with ASTRO Evidence Rating and Strength of
ASTRO Recommendation modifications or qualifying statements in bold italics) Recommendations
Key Question 1 (Part 1): When is it appropriate to add systemic therapy to definitive radiotherapy in the treatment of OPSCC? In the scenario of stage IVA-IVB disease?
ASCO Qualifying Statement: For this version of the
guideline, recommendations for radiation therapy
for OPSCC do not vary by HPV status. Clinical trials
are ongoing to assess the need for risk stratification
in the treatment of OPSCC by HPV status. As such,
these guidelines, though currently accurate, will
likely need to be updated when such evidence
becomes available in the future. In addition, the
staging system that is referenced in these guidelines
is the AJCC, 7th edition. With the implementation
of the AJCC Manual, 8th edition, which is expected
to begin on January 1, 2018, there will be important
changes, such as stage migration due to
reclassification of selected scenarios, and the
divergence of OPSCC into two distinct prognostic
groups based on HPV status. At that transition,
these guidelines must be interpreted in the context
of the two different staging systems.
Recommendation 1A. Concurrent high-dose Recommendation 1A. Concurrent high-dose High-quality evidence, strong recommendation
intermittent cisplatin should be delivered to intermittent cisplatin should be delivered to patients
patients with stage IVA-IVB OPSCC receiving with stage IVA-IVB OPSCC receiving definitive
definitive radiotherapy. radiotherapy.
Recommendation 1B. Concurrent cetuximab or Recommendation 1B. Concurrent cetuximab or High-quality evidence, conditional recommendation
carboplatin-fluorouracil should be delivered to carboplatin-fluorouracil may be delivered to patients
patients with stage IVA-IVB OPSCC receiving with stage IVA-IVB OPSCC receiving definitive
definitive radiotherapy who are not medically fit for radiotherapy who are not medically fit for high-dose
high-dose cisplatin. cisplatin.
Recommendation 1C. Concurrent weekly cisplatin Recommendation 1C. Concurrent weekly cisplatin may Low-quality evidence, conditional recommendation
may be delivered to patients with stage IVA-IVB be delivered to patients with stage IVA-IVB OPSCC
OPSCC receiving definitive radiotherapy who are receiving definitive radiotherapy who are not
not medically fit for high-dose cisplatin, after medically fit for high-dose cisplatin, after a careful
a careful discussion of patient preferences and the discussion of patient preferences and the limited
limited prospective data supporting this regimen. prospective data supporting this regimen.
Recommendation 1D. Concurrent cetuximab should Recommendation 1D. Concurrent cetuximab should High-quality evidence, strong recommendation
not be delivered in combination with chemotherapy not be delivered in combination with chemotherapy
to patients with stage IVA-IVB OPSCC receiving to patients with stage IVA-IVB OPSCC receiving
definitive radiotherapy. definitive radiotherapy.
Recommendation 1E. Intra-arterial chemotherapy Recommendation 1E. Intra-arterial chemotherapy High-quality evidence, strong recommendation
should not be delivered to patients with stage IVA- should not be delivered to patients with stage IVA-IVB
IVB OPSCC receiving definitive radiotherapy. OPSCC receiving definitive radiotherapy.
Key Question 1 (Part 2): When is it appropriate to add systemic therapy to definitive radiotherapy in the treatment of OPSCC? In the scenario of stage III disease:
Recommendation 1F. Concurrent systemic therapy Recommendation 1F. Concurrent systemic therapy Moderate-quality evidence, strong recommendation
should be delivered to patients with T3 N0-1 should be delivered to patients with T3 N0-1 OPSCC
OPSCC receiving definitive radiotherapy. receiving definitive radiotherapy.
Recommendation 1G. Concurrent systemic therapy Recommendation 1G. Concurrent systemic therapy Low-quality evidence, conditional recommendation
may be delivered to patients with T1-T2 N1 may be delivered to patients with T1-T2 N1 OPSCC
OPSCC receiving definitive radiotherapy who are receiving definitive radiotherapy who are considered
considered at particularly significant risk for at particularly significant risk for locoregional
locoregional recurrence, after a careful discussion recurrence, after a careful discussion of patient
of patient preferences and the limited evidence. preferences and the limited evidence.
Key Question 1 (Part 3): When is it appropriate to add systemic therapy to definitive radiotherapy in the treatment of OPSCC? In the scenario of stage I-II disease:
Recommendation 1H. Concurrent systemic Recommendation 1H. Concurrent systemic therapy Low-quality evidence, strong recommendation
therapy should not be delivered to patients should not be delivered to patients with stage I-II
with stage I-II OPSCC receiving definitive OPSCC receiving definitive radiotherapy.
radiotherapy.
Key Question 2 (Part 1): When is it appropriate to deliver postoperative radiotherapy with and without systemic therapy following primary surgery of OPSCC? In the
scenario of positive margins and/or extracapsular nodal extension:
Recommendation 2A. Concurrent high-dose Recommendation 2A. Concurrent high-dose Moderate-quality evidence, strong recommendation
intermittent cisplatin should be delivered with intermittent cisplatin should be delivered with
postoperative radiotherapy to patients with positive postoperative radiotherapy to patients with
surgical margins and/or extracapsular nodal positive surgical margins and/or extracapsular
extension; this high-risk population includes nodal extension; this high-risk population includes
patients independent of HPV status or the extent of patients independent of HPV status or the extent
extranodal tumor. of extranodal tumor.
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 Quon et al

Table 1. Original ASTRO and ASCO Endorsement Research Questions, Recommendations, and Qualifying Statements (continued)
ASCO Endorsement Recommendation (with ASTRO Evidence Rating and Strength of
ASTRO Recommendation modifications or qualifying statements in bold italics) Recommendations
Recommendation 2B. Concurrent weekly cisplatin Recommendation 2B. Concurrent weekly cisplatin may Low-quality evidence, conditional recommendation
may be delivered with postoperative radiotherapy be delivered with postoperative radiotherapy to
to patients who are considered inappropriate for patients who are considered inappropriate for
standard high-dose intermittent cisplatin after standard high-dose intermittent cisplatin after
a careful discussion of patient preferences and the a careful discussion of patient preferences and the
limited evidence supporting this treatment limited evidence supporting this treatment schedule.
schedule.
Recommendation 2C. For the high-risk postoperative Recommendation 2C. For the high-risk postoperative Moderate-quality evidence, strong recommendation
patient unable to receive cisplatin-based concurrent patient unable to receive cisplatin-based concurrent
chemoradiotherapy, radiotherapy alone should be chemoradiotherapy, radiotherapy alone should be
routinely delivered without concurrent systemic routinely delivered without concurrent systemic
therapy; given the limited evidence supporting therapy; given the limited evidence supporting
alternative regimens, treatment with noncisplatin alternative regimens, treatment with noncisplatin
systemic therapy should be accompanied by systemic therapy should be accompanied by a careful
a careful discussion of the risks and unknown discussion of the risks and unknown benefits of the
benefits of the combination. combination.
Recommendation 2D. Patients treated with Recommendation 2D. Patients treated with Moderate-quality evidence, strong recommendation
postoperative radiotherapy should not receive postoperative radiotherapy should not receive
concurrent weekly carboplatin. concurrent weekly carboplatin.
Recommendation 2E. Patients treated with Recommendation 2E. Patients treated with Low-quality evidence, strong recommendation
postoperative radiotherapy should not receive postoperative radiotherapy should not receive
cetuximab, either alone or in combination with cetuximab, either alone or in combination with
chemotherapy, although such regimens are chemotherapy, although such regimens are currently
currently under investigation. under investigation.
Recommendation 2F. Patients treated with Recommendation 2F. Patients treated with Low-quality evidence, strong recommendation
postoperative radiotherapy should not routinely postoperative radiotherapy should not routinely
receive concurrent weekly docetaxel given the receive concurrent weekly docetaxel given the
limited evidence supporting its use, although such limited evidence supporting its use, although such
regimens are currently under investigation. regimens are currently under investigation.
Recommendation 2G. Patients treated with Recommendation 2G. Patients treated with Moderate-quality evidence, strong recommendation
postoperative radiotherapy should not receive postoperative radiotherapy should not receive
concurrent mitomycin-C, alone or with bleomycin, concurrent mitomycin-C, alone or with bleomycin,
given the limited evidence and experience given the limited evidence and experience supporting
supporting its use. its use.
Recommendation 2H. Postoperative chemotherapy Recommendation 2H. Postoperative chemotherapy High-quality evidence, strong recommendation
should not be delivered alone or sequentially with should not be delivered alone or sequentially with
postoperative radiotherapy. postoperative radiotherapy.
Key Question 2 (Part 2): When is it appropriate to deliver postoperative radiotherapy with and without systemic therapy following primary surgery of OPSCC? In the
scenario of intermediate-risk pathologic factors, such as LVI, PNI, T3-4 disease, or positive lymph nodes:
Recommendation 2I. Patients with intermediate risk Recommendation 2I. Patients with intermediate Moderate-quality evidence, strong recommendation
factors should not routinely receive concurrent risk factors should not routinely receive
systemic therapy with postoperative radiotherapy. concurrent systemic therapy with postoperative
radiotherapy.
Recommendation 2J. Patients with intermediate-risk Recommendation 2J. Patients with intermediate-risk Low-quality evidence, conditional recommendation
factors whose surgical procedure and/or pathologic factors whose surgical procedure and/or pathologic
findings imply a particularly significant risk of findings imply a particularly significant risk of
locoregional recurrence may receive concurrent locoregional recurrence may receive concurrent
cisplatin-based chemotherapy after a careful cisplatin-based chemotherapy after a careful
discussion of patient preferences and the limited discussion of patient preferences and the limited
evidence supporting its use in this scenario; evidence supporting its use in this scenario;
alternative systemic treatment regimens should alternative systemic treatment regimens should only
only be used in the context of a clinical trial. be used in the context of a clinical trial.
Recommendation 2K. Postoperative radiotherapy Recommendation 2K. Postoperative radiotherapy Low-quality evidence, strong recommendation
should be delivered to patients with pathologic should be delivered to patients with pathologic T3 or
T3 or T4 disease. T4 disease.
Recommendation 2L. Postoperative radiotherapy Recommendation 2L. Postoperative radiotherapy Low-quality evidence, strong recommendation
should be delivered to patients with pathologic should be delivered to patients with pathologic N2 or
N2 or N3 disease. N3 disease.
Recommendation 2M. Postoperative radiotherapy Recommendation 2M. Postoperative radiotherapy may Low-quality evidence, conditional recommendation
may be delivered to patients with pathologic be delivered to patients with pathologic N1 disease
N1 disease after a careful discussion of after a careful discussion of patient preferences and
patient preferences and the limited evidence the limited evidence of outcomes following surgery
of outcomes following surgery alone in this alone in this scenario.
scenario.
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 Radiation Therapy for Oropharyngeal Squamous Cell Carcinoma Guideline

Table 1. Original ASTRO and ASCO Endorsement Research Questions, Recommendations, and Qualifying Statements (continued)
ASCO Endorsement Recommendation (with ASTRO Evidence Rating and Strength of
ASTRO Recommendation modifications or qualifying statements in bold italics) Recommendations
Recommendation 2N. Postoperative radiotherapy Recommendation 2N. Postoperative radiotherapy may Low-quality evidence, conditional recommendation
may be delivered to patients with LVI and/or PNI as be delivered to patients with LVI and/or PNI as the
the only risk factor(s) after a careful discussion of only risk factor(s) after a careful discussion of patient
patient preferences and the limited evidence of preferences and the limited evidence of outcomes
outcomes following surgery alone in this scenario. following surgery alone in this scenario.
Key Question 2 (Part 3): When is it appropriate to deliver postoperative radiotherapy with and without systemic therapy following primary surgery of OPSCC? In the
scenario of no pathologic factors:
Recommendation 2O. Postoperative radiotherapy Recommendation 2O. Postoperative radiotherapy may Low-quality evidence, conditional recommendation
may be delivered to patients without conventional be delivered to patients without conventional adverse
adverse pathologic risk factors only if the clinical pathologic risk factors only if the clinical and surgical
and surgical findings imply a particularly significant findings imply a particularly significant risk of
risk of locoregional recurrence, after a careful locoregional recurrence, after a careful discussion of
discussion of patient preferences and the potential patient preferences and the potential harms and
harms and benefits of radiotherapy. benefits of radiotherapy.
Key Question 3: When is it appropriate to use induction chemotherapy in the treatment of OPSCC?
Recommendation 3A. Induction chemotherapy Recommendation 3A. Induction chemotherapy should High-quality evidence, strong recommendation
should not be routinely delivered to patients with not be routinely delivered to patients with OPSCC.
OPSCC.
Key Question 4 (Part 1): What are the appropriate dose, fractionation, and volume regimens with and without systemic therapy in the treatment of OPSCC? In the
scenario of definitive nonsurgical therapy:
Recommendation 4A. A dose of 70 Gy over 7 weeks Recommendation 4A. A dose of 70 Gy over 7 weeks Moderate-quality evidence, strong recommendation
should be delivered to gross primary and nodal should be delivered to gross primary and nodal
disease in patients with stage III-IV OPSCC disease in patients with stage III-IV OPSCC selected
selected to receive standard, once-daily definitive to receive standard, once-daily definitive
radiotherapy. radiotherapy.
Recommendation 4B. The biologically equivalent Recommendation 4B. The biologically equivalent dose Low-quality evidence, strong recommendation
dose of approximately 50 Gy in 2 Gy fractions or of approximately 50 Gy in 2 Gy fractions or slightly
slightly higher should be delivered electively to higher should be delivered electively to clinically and
clinically and radiographically negative regions at radiographically negative regions at risk for
risk for microscopic spread of tumor. microscopic spread of tumor.
Recommendation 4C. Altered fractionation should be Recommendation 4C. Altered fractionation should be High-quality evidence, strong recommendation
used in patients with stage IVA-IVB OPSCC treated used in patients with stage IVA-IVB OPSCC treated
with definitive radiotherapy who are not receiving with definitive radiotherapy who are not receiving
concurrent systemic therapy. concurrent systemic therapy.
Recommendation 4D. Either accelerated Recommendation 4D. Either accelerated radiotherapy High-quality evidence, conditional recommendation
radiotherapy or hyperfractionated radiotherapy may or hyperfractionated radiotherapy may be used in
be used in patients with OPSCC treated with patients with OPSCC treated with altered
altered fractionation definitive radiotherapy after fractionation definitive radiotherapy after a careful
a careful discussion of patient preferences and the discussion of patient preferences and the limited
limited evidence supporting one regimen over the evidence supporting one regimen over the other.
other.
Recommendation 4E. Either standard, once-daily Recommendation 4E. Either standard, once-daily High-quality evidence, conditional recommendation
radiotherapy or accelerated fractionation may be radiotherapy or accelerated fractionation may be used
used when treating OPSCC with concurrent when treating OPSCC with concurrent systemic
systemic therapy after a careful discussion of therapy after a careful discussion of patient
patient preferences and the risks and benefits of preferences and the risks and benefits of both
both approaches. approaches.
ASCO qualifying statement: In the Danish Head and
Neck Cancer Group randomized controlled trial of
1,485 patients with squamous cell carcinoma of
the head and neck (larynx, pharynx, and oral
cavity), standard radiotherapy was defined as 66-
68 Gy, delivered in 2-Gy fractions, five fractions
per week, compared with the accelerated arm,
which received the same dose at a rate of six
fractions per week, resulting in the same dose
delivered over 7 or 6 weeks, respectively.4
Recommendation 4F. Altered fractionation should be Recommendation 4F. Altered fractionation should be Moderate-quality evidence, strong recommendation
used in patients with T3 N0-1 OPSCC treated with used in patients with T3 N0-1 OPSCC treated with
definitive radiotherapy who do not receive definitive radiotherapy who do not receive concurrent
concurrent systemic therapy. systemic therapy.
Recommendation 4G. Altered fractionation may be Recommendation 4G. Altered fractionation may be Low-quality evidence, conditional recommendation
used in patients with T1-2 N1 or T2 N0 OPSCC used in patients with T1-2 N1 or T2 N0 OPSCC treated
treated with definitive radiotherapy alone who are with definitive radiotherapy alone who are considered
considered at particularly significant risk of at particularly significant risk of locoregional
locoregional recurrence, after a careful discussion recurrence, after a careful discussion of patient
of patient preferences and the limited evidence preferences and the limited evidence supporting its
supporting its use in this scenario. use in this scenario.
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 Quon et al

Table 1. Original ASTRO and ASCO Endorsement Research Questions, Recommendations, and Qualifying Statements (continued)
ASCO Endorsement Recommendation (with ASTRO Evidence Rating and Strength of
ASTRO Recommendation modifications or qualifying statements in bold italics) Recommendations
Key Question 4 (Part 2): What are the appropriate dose, fractionation, and volume regimens with and without systemic therapy in the treatment of OPSCC? In the
scenario of adjuvant postoperative radiotherapy:
Recommendation 4H. Adjuvant postoperative Recommendation 4H. Adjuvant postoperative Moderate-quality evidence, strong recommendation
radiotherapy should be delivered to regions of radiotherapy should be delivered to regions of
microscopically positive primary site surgical microscopically positive primary site surgical margins
margins and extracapsular nodal extension at 2 Gy/ and extracapsular nodal extension at 2 Gy/fraction
fraction once daily to a total dose between 60 and once daily to a total dose between 60 and 66 Gy.
66 Gy.
Recommendation 4I. Adjuvant postoperative Recommendation 4I. Adjuvant postoperative Low-quality evidence, conditional recommendation
radiotherapy delivered without concurrent radiotherapy delivered without concurrent systemic
systemic therapy should treat regions of therapy should treat regions of microscopically
microscopically positive primary site surgical positive primary site surgical margins and
margins and extracapsular nodal extension at 2 Gy/ extracapsular nodal extension at 2 Gy/fraction once
fraction once daily to a total dose of 66 Gy, although daily to a total dose of 60-66 Gy, although there are
there are limited data guiding this recommendation. limited data guiding this recommendation.
ASCO qualifying statement: In the setting of single-
modality postoperative radiotherapy, the time
from surgery to the completion of radiotherapy
should be kept as short as possible, ideally < 85
day, as the time to completion of postoperative
radiotherapy may be the most important
radiotherapy factor and not the dose per se.
Recommendation 4J. Adjuvant postoperative Recommendation 4J. Adjuvant postoperative Moderate-quality evidence, strong recommendation
radiotherapy should be delivered to the tumor bed radiotherapy should be delivered to the tumor bed
and involved, dissected lymph node regions at 2 and involved, dissected lymph node regions at once
Gy/fraction once daily to a total dose of 60 Gy in the daily fractionation to a total dose of 56-60 Gy in the
absence of primary site positive margins and absence of primary site positive margins and
extracapsular nodal extension. extracapsular nodal extension.
Key Question 4 (Part 3): What are the appropriate dose, fractionation, and volume regimens with and without systemic therapy in the treatment of OPSCC? In the
scenario of early T-stage tonsillar carcinoma:
Recommendation 4K. Unilateral radiotherapy should Recommendation 4K. Unilateral radiotherapy should be Moderate-quality evidence, strong recommendation
be delivered to patients with well-lateralized (no delivered to patients with well-lateralized (no soft
soft palate extension or base of tongue palate extension or base of tongue involvement), T1-
involvement), T1-T2 tonsillar cancer and N0-N1 T2 tonsillar cancer and N0-N1 nodal category.
nodal category.
Recommendation 4L. Unilateral radiotherapy may be Recommendation 4L. Unilateral radiotherapy may be Low-quality evidence, conditional recommendation
delivered to patients with lateralized (, 1 cm of soft delivered to patients with lateralized (, 1 cm of soft
palate extension but without base of tongue palate extension but without base of tongue
involvement) T1-T2 N0-N2a tonsillar cancer without involvement) T1-T2 N0-N2b tonsillar cancer without
clinical or radiographic evidence of extracapsular clinical or radiographic evidence of extracapsular
extension, after careful discussion of patient extension, after careful discussion of patient
preferences and the relative benefits of unilateral preferences and the relative benefits of unilateral
treatment versus the potential for contralateral treatment versus the potential for contralateral nodal
nodal recurrence and subsequent salvage recurrence and subsequent salvage treatment.
treatment.

Abbreviations: AJCC, American Joint Committee on Cancer Staging Manual; ASTRO, American Society for Radiation Oncology; HPV, human papillomavirus; LVI,
lymphovascular invasion; OPSCC, oropharyngeal squamous cell carcinoma; PNI, perineural invasion.

plus 2 Gy per day, 5 days/week for 4.5 weeks; total dose, 68 Gy) and
conventional fractionation (2 Gy per day, 5 days/week for 7 weeks;
total dose, 68 Gy), were available. The results of the 2-year report,
which failed to show a positive effect resulting from accelerated
fractionation for LRC, OS, and cancer-specific survival, were
confirmed in the update with mature 5-year follow-up data.9
DISCUSSION
Endorsement Recommendation
ASCO endorses the ASTRO Radiation Therapy for Oro-
pharyngeal Squamous Cell Carcinoma Evidence-Based Clinical
Practice Guideline, with minor ASCO Expert Panel statements
(Table 1). The ASTRO Guidelines Subcommittee chose to un-
dertake a guideline on OPSCC because of its rising prevalence and
potential for treatment-related toxicities and because it provides
many challenges to radiation oncologists, as well as medical and
surgical oncologists who comprise the multidisciplinary team. At
this time, ASTRO does not have plans to produce guidelines for
other subsites of squamous cell carcinoma of the head and neck.
The ASCO Endorsement Panel (Appendix Table A1, online only)
agreed that these recommendations would be a timely and useful
resource for practitioners who treat individuals with OPSCC.
ASCO added very minor modifications to the recommendations,
such as providing a range to the intensity of radiation therapy in the
scenario of adjuvant postoperative radiation therapy, to reflect the
lack of precision of the evidence base. In addition, qualifying
statements were added to clarify the definition of accelerated ra-
diotherapy and the importance of the total time from surgery to the
completion of radiotherapy.
The ASCO Expert Panel also noted that the importance
of the individualization of therapy in this complex disease,
based on patients’ comorbidities and preferences, as most of

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 Radiation Therapy for Oropharyngeal Squamous Cell Carcinoma Guideline

guidelines, though currently accurate, will likely need to be updated

Related ASCO Guidelines
• Head and Neck Cancer Survivorship Care10 (http://
ascopubs.org/doi/full/10.1200/JCO.2016.71.8478)
• Integration of Palliative Care Into Standard Oncology
Practice11 (http://ascopubs.org/doi/full/10.1200/JCO.
2016.70.1474)
• Management of Chronic Pain in Survivors of Adult
Cancers12 (http://ascopubs.org/doi/full/10.1200/JCO.
2016.68.5206)
• Screening, Assessment, and Management of Fatigue in
Adult Survivors of Cancer13 (http://ascopubs.org/doi/
full/10.1200/JCO.2013.53.4495)
• Screening, Assessment, and Care of Anxiety and
Depressive Symptoms in Adults With Cancer14 (http://
ascopubs.org/doi/full/10.1200/JCO.2013.52.4611)
when such evidence becomes available in the future. Lastly, it is
noteworthy that staging information referenced in these guidelines is
based on the American Joint Committee on Cancer Staging Manual,
7th edition. With the implementation of the American Joint
Committee on Cancer Manual, 8th edition, which is expected to
begin on January 1, 2018, there will be important changes such as
stage migration due to reclassification of selected scenarios and the
divergence of OPSCC into two distinct prognostic groups based on
HPV status. At that transition, these guidelines must be interpreted
in the context of the two different staging systems.
ADDITIONAL RESOURCES
More information, including a Data Supplement, a Methodology
Supplement, slide sets, and clinical tools and resources, is available
at www.asco.org/head-neck-cancer-guidelines and www.asco.org/
guidelineswiki. Patient information is available at www.cancer.net.
Visit www.asco.org/guidelineswiki to provide comments on the
guideline or to submit new evidence.

the recommendations were made based on efficacy results with AUTHORS’ DISCLOSURES OF POTENTIAL CONFLICTS
relatively little quality of life or patient-reported outcomes data in OF INTEREST
the literature. These guidelines also did not specifically address
the types of primary surgery undertaken for OPSCC and their Disclosures provided by the authors are available with this article at
impact on the delivery of postoperative radiotherapy or CRT. For jco.org.
example, the utility of transoral robotic surgery as part of the
treatment armamentaria of OPSCC is being evaluated in ongoing
clinical trials. In addition, although the guidelines explicitly state AUTHOR CONTRIBUTIONS
that recommendation statements do not vary by HPV status, it is
relevant to point out that clinical trials are ongoing to assess the need Manuscript writing: All authors
for risk stratification in the treatment of OPSCC. As such, these Final approval of manuscript: All authors

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 Quon et al

Affiliations
Harry Quon and Arlene Forastiere, Johns Hopkins University School of Medicine, Baltimore, MD; Neha Vapiwala, Perelman School
of Medicine, University of Pennsylvania, Philadelphia, PA; Erin B. Kennedy, American Society of Clinical Oncology, Alexandria, VA;
David J. Adelstein, Taussig Cancer Institute, Cleveland, OH; Holly Boykin, Head and Neck Cancer Alliance, Charleston, SC; Joseph A.
Califano, University of California San Diego Medical Center, San Diego; F. Chris Holsinger, Stanford University Medical Center, Palo Alto,
CA; Brian Nussenbaum, Washington University School of Medicine, St. Louis, MO; David I. Rosenthal, The University of Texas MD
Anderson Cancer Center, Houston TX; and Lillian L. Siu and John N. Waldron, Princess Margaret Cancer Centre, Toronto, Canada.

nnn

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 Radiation Therapy for Oropharyngeal Squamous Cell Carcinoma Guideline

AUTHORS’ DISCLOSURES OF POTENTIAL CONFLICTS OF INTEREST

Radiation Therapy for Oropharyngeal Squamous Cell Carcinoma: American Society of Clinical Oncology Endorsement of the American Society for
Radiation Oncology Evidence-Based Clinical Practice Guideline
The following represents disclosure information provided by authors of this manuscript. All relationships are considered compensated. Relationships are
self-held unless noted. I = Immediate Family Member, Inst = My Institution. Relationships may not relate to the subject matter of this manuscript. For more
information about ASCO’s conflict of interest policy, please refer to www.asco.org/rwc or ascopubs.org/jco/site/ifc.
Harry Quon F. Chris Holsinger
Consulting or Advisory Role: Concordia/Pinnacle Biologics No relationship to disclose
Research Funding: Toshiba America Research, VibrentHealth
Patents, Royalties, Other Intellectual Property: Filed under Hopkins, Brian Nussenbaum
we have several patents related to mobile informatics solutions No relationship to disclose

Neha Vapiwala David I. Rosenthal

Consulting or Advisory Role: Bayer Stock or Other Ownership: Concordia Pharmaceuticals
Honoraria: Merck Serono
Arlene Forastiere Consulting or Advisory Role: Merck Serono
Stock or Other Ownership: NantHealth Research Funding: Merck Serono
Travel, Accommodations, Expenses: Merck Serono
Erin B. Kennedy
No relationship to disclose Lillian L. Siu
Leadership: Agios (I)
David J. Adelstein Consulting or Advisory Role: Boehringer Ingelheim, Merck, AstraZeneca/
No relationship to disclose MedImmune, Celgene, Pfizer
Holly Boykin Research Funding: Bristol-Myers Squibb, Genentech/Roche,
Honoraria: Eli Lilly, AstraZeneca GlaxoSmithKline, Merck, Novartis, Pfizer, MedImmune, AstraZeneca,
Travel, Accommodations, Expenses: AstraZeneca Boehringer Ingelheim, Bayer, Amgen

Joseph A. Califano John N. Waldron

No relationship to disclose No relationship to disclose

jco.org © 2017 by American Society of Clinical Oncology

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 Quon et al

Acknowledgment

The Expert Panel thanks Eben Rosenthal, MD, and Abhishek Tripathi, MD, and the Clinical Practice Guidelines Committee for their
thoughtful reviews and insightful comments on this guideline endorsement.

Appendix

Table A1. Guideline Endorsement Panel Membership

Name Affiliation
Arlene Forastiere, MD, co-chair Johns Hopkins University School of Medicine, Baltimore, MD
Neha Vapiwala, MD, co-chair and Practice Guidelines Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA
Implementation Network representative
Harry Quon, MD, co-chair Johns Hopkins University School of Medicine, Baltimore, MD
David J. Adelstein, MD Taussig Cancer Institute, Cleveland, OH
Holly Boykin, patient representative Head and Neck Cancer Alliance, Charleston, SC
Joseph A. Califano, MD University of California San Diego Medical Center, San Diego, CA
F. Chris Holsinger, MD Stanford University Medical Center, Palo Alto, CA
Brian Nussenbaum, MD Washington University School of Medicine, St. Louis, MO
David I. Rosenthal, MD The University of Texas MD Anderson Cancer Center, Houston, TX
Lillian L. Siu, MD Princess Margaret Cancer Centre, Toronto, Canada
John N. Waldron, MD Princess Margaret Cancer Centre, Toronto, Canada

NOTE. ASCO staff: Erin B. Kennedy, MHSc.

© 2017 by American Society of Clinical Oncology JOURNAL OF CLINICAL ONCOLOGY

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