This is the current release of the guideline.

Early- and intermediate-stage squamous cell carcinoma (SCCA) of the tonsil

To evaluate the appropriateness of radiologic treatment procedures for early- and intermediate-stage squamous cell carcinoma of the tonsil

Patients with early- and intermediate-stage squamous cell carcinoma of the tonsil

Radiation Therapy Volume

1. Ipsilateral neck irradiation plus primary
2. Bilateral neck irradiation plus primary

Contralateral nodal failure

Literature Search Procedure

The Medline literature search is based on keywords provided by the topic author. The two general classes of keywords are those related to the condition (e.g., ankle pain, fever) and those that describe the diagnostic or therapeutic intervention of interest (e.g., mammography, MRI).

The search terms and parameters are manipulated to produce the most relevant, current evidence to address the American College of Radiology Appropriateness Criteria (ACR AC) topic being reviewed or developed. Combining the clinical conditions and diagnostic modalities or therapeutic procedures narrows the search to be relevant to the topic. Exploding the term "diagnostic imaging" captures relevant results for diagnostic topics.

The following criteria/limits are used in the searches.

1. Articles that have abstracts available and are concerned with humans.
2. Restrict the search to the year prior to the last topic update or in some cases the author of the topic may specify which year range to use in the search. For new topics, the year range is restricted to the last 5 years unless the topic author provides other instructions.
3. May restrict the search to Adults only or Pediatrics only.
4. Articles consisting of only summaries or case reports are often excluded from final results.

The search strategy may be revised to improve the output as needed.

The total number of source documents identified as the result of the literature search is not known.

Strength of Evidence Key

Category 1 - The conclusions of the study are valid and strongly supported by study design, analysis and results.

Category 2 - The conclusions of the study are likely valid, but study design does not permit certainty.

Category 3 - The conclusions of the study may be valid but the evidence supporting the conclusions is inconclusive or equivocal.

Category 4 - The conclusions of the study may not be valid because the evidence may not be reliable given the study design or analysis

The topic author drafts or revises the narrative text summarizing the evidence found in the literature. American College of Radiology (ACR) staff draft an evidence table based on the analysis of the selected literature. These tables rate the strength of the evidence for all articles included in the narrative text.

The expert panel reviews the narrative text, evidence table, and the supporting literature for each of the topic-variant combinations and assigns an appropriateness rating for each procedure listed in the table. Each individual panel member forms his/her own opinion based on his/her interpretation of the available evidence.

More information about the evidence table development process can be found in the American College of Radiology (ACR) Appropriateness Criteria® Evidence Table Development document (see the "Availability of Companion Documents" field).

Modified Delphi Technique

The appropriateness ratings for each of the procedures included in the Appropriateness Criteria topics are determined using a modified Delphi methodology. A series of surveys are conducted to elicit each panelist's expert interpretation of the evidence, based on the available data, regarding the appropriateness of an imaging or therapeutic procedure for a specific clinical scenario. American College of Radiology (ACR) staff distributes surveys to the panelists along with the evidence table and narrative. Each panelist interprets the available evidence and rates each procedure. The surveys are completed by panelists without consulting other panelists. The ratings are a scale between 1 and 9, which is further divided into three categories: 1, 2, or 3 is defined as "usually not appropriate"; 4, 5, or 6 is defined as "may be appropriate"; and 7, 8, or 9 is defined as "usually appropriate." Each panel member assigns one rating for each procedure per survey round. The surveys are collected and the results are tabulated, de-identified and redistributed after each round. A maximum of three rounds are conducted. The modified Delphi technique enables each panelist to express individual interpretations of the evidence and his or her expert opinion without excessive bias from fellow panelists in a simple, standardized and economical process.

Consensus among the panel members must be achieved to determine the final rating for each procedure. Consensus is defined as eighty percent (80%) agreement within a rating category. The final rating is determined by the median of all the ratings once consensus has been reached. Up to three rating rounds are conducted to achieve consensus.

If consensus is not reached, the panel is convened by conference call. The strengths and weaknesses of each imaging procedure that has not reached consensus are discussed and a final rating is proposed. If the panelists on the call agree, the rating is accepted as the panel's consensus. The document is circulated to all the panelists to make the final determination. If consensus cannot be reached on the call or when the document is circulated, "No consensus" appears in the rating column and the reasons for this decision are added to the comment sections.

Not applicable

A formal cost analysis was not performed and published cost analyses were not reviewed.

Criteria developed by the Expert Panels are reviewed by the American College of Radiology (ACR) Committee on Appropriateness Criteria.

ACR Appropriateness Criteria®

Clinical Condition: Ipsilateral Radiation for Squamous Cell Carcinoma of the Tonsil

Variant 1: 50-year-old man with a T2N0 SCCA of the right tonsil, with tumor extending 0.5 cm onto the soft palate. There is no base of tongue involvement. HPV status is negative.

Note: Abbreviations used in the tables are listed at the end of the "Major Recommendations" field.

Variant 2: 50-year-old man with a T3N0 SCCA of the right tonsil, with tumor extending 1 cm onto the soft palate (2 cm from midline). There is no base of tongue involvement. HPV status is negative.

Note: Abbreviations used in the tables are listed at the end of the "Major Recommendations" field.

Variant 3: 50-year-old man with a T3N0 SCCA of the right tonsil, with tumor extending onto the soft palate to within 1 cm of midline. There is no base of tongue involvement. HPV status is negative.

Note: Abbreviations used in the tables are listed at the end of the "Major Recommendations" field.

Variant 4: 50-year-old man with a T1N1 SCCA of the right tonsil, with no soft palate or base of tongue extension. There is a single positive node in right level II. HPV status is negative.

Note: Abbreviations used in the tables are listed at the end of the "Major Recommendations" field.

Variant 5: 50-year-old with a T1N2b SCCA of the right tonsil, with no soft palate or base of tongue extension. There are two positive nodes located in right level II. HPV status is negative.

Note: Abbreviations used in the tables are listed at the end of the "Major Recommendations" field.

Variant 6: 50-year-old man with a T2N1 SCCA of the right tonsil, with no soft palate or base of tongue extension. HPV status is positive.

Note: Abbreviations used in the tables are listed at the end of the "Major Recommendations" field.

Summary of Literature Review

Introduction

Treatment of early- and intermediate-stage carcinoma of the palatine tonsil with primary radiotherapy (RT) has a high success rate. The well-lateralized location of the tonsils means that squamous cell carcinomas (SCCAs) arising in this region rarely metastasize to lymph nodes in the contralateral hemineck. Because of this finding, multiple reports have questioned the need to electively irradiate the clinically negative contralateral hemineck in selected patients. Controversy exists, however, as to the specific criteria for selecting patients for ipsilateral RT (defined as radiation to the primary site and ipsilateral regional nodes only). Important factors in determining the appropriateness of ipsilateral radiation are T stage, N stage, and the extent of invasion of the soft palate and base of tongue. Appropriate patient selection is a critical issue, as regional recurrences are rarely successfully salvaged. The benefit of limiting radiation to the ipsilateral hemineck is decreasing the rate of permanent xerostomia, a condition that often results in poor nutrition and accelerated tooth decay, as well as decreased quality of life. This article specifically discusses the appropriate RT volume without addressing the role of systemic chemotherapy concurrent with radiation.

Results from Surgical Literature

Although there are multiple reports on the outcome of tonsillar carcinoma treated with primary surgery, only a few specifically address the rate of neck failure in the undissected and unirradiated contralateral neck. The Mayo Clinic published its results on 56 patients with stage T1-4 N0-2b SCCA of the tonsil who underwent surgery alone. Seventy-nine percent of patients were stage T1-2, and 88% were N0-1. All patients underwent resection of the primary tumor, and 75% underwent an ipsilateral neck dissection. No patient had a dissection of the contralateral neck. With a minimum follow-up of 3.5 years, 3 of the 56 patients (5%) failed in the contralateral neck, with control at the primary and ipsilateral neck.

Multiple pathologic studies have shown that, for tonsillar primaries, the risk of pathologically occult contralateral lymph nodes is about 15% overall, and depends on the extent of the primary tumor and clinical N stage. Patients with T1-2 N0-1 tonsillar cancers have an extremely low risk of pathologically positive contralateral nodes, supporting the use of ipsilateral RT techniques in these patients.

One study retrospectively analyzed 43 patients with SCCA of the tonsil who underwent elective dissection of the clinically negative contralateral hemineck. The rate of pathologically positive contralateral lymph nodes was 16% in the entire patient cohort, with none occurring in the 10 patients who were N0. Six of the seven patients with pathologically positive contralateral nodes were T3 or T4. No attempt was made to correlate the results with extent of soft palate or base of tongue invasion.

Another study reviewed 197 patients with SCCA of the tonsil who underwent bilateral neck dissections and showed that 14.7% had pathologically positive contralateral lymph nodes, although the authors did not specify the clinical stage of the contralateral hemineck prior to neck dissection.

A recent report from Korea showed that 2 of 21 (9.5%) patients with SCCA of the tonsil who underwent an elective contralateral neck dissection in addition to resection of the primary and ipsilateral neck dissection had pathologically positive contralateral nodes. These 2 patients were clinically N+, but the report did not specify the exact N stage. None of the patients who were clinically N0 had pathologically involved contralateral nodes.

Extent of Soft Palate or Base of Tongue Invasion

The extent of invasion of the primary tonsillar tumor into the soft palate and base of tongue has been shown to be an important predictor of contralateral lymph node failure. As tumor approaches midline in the base of tongue or soft palate, the risk of contralateral nodal involvement increases.

The seminal study on ipsilateral RT for tonsillar carcinoma is a retrospective study from the Princess Margaret Hospital group which reported the outcomes of 228 patients with carcinoma of the tonsil treated with ipsilateral RT techniques. All patients had a clinically negative contralateral hemineck. The majority of patients were treated to 50 Gy at 2.5 Gy per fraction using cobalt 60. Contralateral neck failure occurred in 8 (3.5%) patients, although only three occurred in patients with control at the primary site. Of the 3 patients who experienced failure in the contralateral neck with the primary controlled, all had significant soft palate involvement (to within 1 cm of midline in 2 cases, and involving the middle third of the palate hemistructure in the third case). Two of the 3 patients were T3, and one was T2. All 3 patients were also N1. No patient with T1 or N0 disease failed in the contralateral neck. The authors concluded that <1 cm of extension into the soft palate or base of tongue is associated with a low risk of occult contralateral nodal involvement and is appropriately treated with ipsilateral RT.

A much smaller study showed excellent contralateral neck control when patients with only minimal soft palate or base of tongue extension were selected for ipsilateral radiation. The study reported on 8 patients with tonsillar carcinoma who had <1 cm of tumor extension to the soft palate or base of tongue and were treated with ipsilateral RT to a total dose of 66-70 Gy at 2 Gy per fraction to the primary tumor. The nodal stage varied from N0-2b. No contralateral neck failures were detected at 5 years.

Other authors have demonstrated that even tumors with more extensive base of tongue or soft palate invasion are successfully treated with ipsilateral radiation. A group of researchers reported on 32 patients with carcinoma of the tonsil or soft palate treated with ipsilateral RT. The only selection criterion was that the primary tumor did not cross midline. The stage varied from T1-4 and N0-3. Patients were treated to 65 Gy plus a 15 Gy boost, depending on clinical response, delivered at 2.5 Gy per fraction using cobalt 60. Eight node-positive patients received bilateral lower neck irradiation. Twelve patients received concurrent carboplatin. The authors found no isolated contralateral neck failures at a median follow-up of 44 months (see Variant 1, Variant 2 and Variant 3 above).

Nodal Stage

The extent of ipsilateral nodal disease has also been correlated with the risk of contralateral nodal failure. Patients with lateralized tumors that are N0-1 have a very low risk of failure in the untreated contralateral hemineck. Controversy exists, however, over the risk for patients with N2 disease, especially N2b.

A prospective study was performed that specifically addressed the issue of the node-positive patient. Twenty patients with carcinoma of the tonsil with stage T1-3 N1-2b were treated with ipsilateral RT. Thirteen of 20 patients were stage N2b. Patients with any invasion of the soft palate or base of tongue were excluded. All patients underwent pretreatment scans with computed tomography (CT) and positron emission tomography using fluorine-18-2-deoxy-D-glucose tracer (FDG-PET) to rule out occult contralateral neck lymphadenopathy. Sixteen of the 20 patients were treated with a tonsillectomy with a resultant positive margin, and 14 had undergone ipsilateral neck dissection prior to ipsilateral RT. Four patients with N2a or large N2b disease were treated with neoadjuvant chemotherapy followed by a planned neck dissection. Nineteen of the 20 patients received chemotherapy, which was concurrent platinum-based chemotherapy in most cases. The total RT dose was 60-66 Gy to the primary tumor or tumor bed for patients treated post-operatively and 66-70 Gy for the four patients treated with primary RT. At a median follow-up of 19 months, there were no contralateral nodal failures.

Another study retrospectively reviewed the charts of 178 patients with carcinoma of the tonsil treated with ipsilateral RT. The majority of patients received 60 Gy at 2.4 Gy per fraction. In 155 patients with stage N0-1 and control at the primary site, only 4 (2.6%) had isolated contralateral nodal failures. The authors did not analyze the contralateral nodal failures in the small number of N2-3 patients (see Variant 4 and Variant 5 above).

Role of Human Papilloma Virus (HPV) Status

HPV-associated SCCA of the oropharynx is thought to be a distinct epidemiologic, clinical, and molecular entity from non-HPV-associated tumors. Given these differences, specific attention has recently been given to determining if ipsilateral RT is appropriate in HPV-associated tonsillar tumors.

A group of researchers reviewed the charts of 41 patients with T1-2 SCCA of the tonsil to assess the rate of radiographically positive contralateral nodes. Patients with any soft palate or base of tongue invasion were excluded. Of the 28 patients with p16+ tumors, 25% presented with contralateral nodal disease. None of the 13 patients with p16– tumors had contralateral nodal disease. The authors conclude that given the high rate of clinically involved nodes in patients with p16+ tumors, the subclinical rate of contralateral nodal involvement may be sufficiently high to warrant elective irradiation of the contralateral hemineck, even in early-stage disease with no extension to the base of tongue or soft palate (see Variant 6 above).

Radiation Technique

Ipsilateral RT can be done with either a 3-dimensional (3D)-conformal wedge-pair photon beam technique or intensity-modulated radiation therapy (IMRT). Both techniques achieve a low mean dose to the contralateral parotid gland, which is the main benefit in using ipsilateral RT. The benefit of using a wedge-pair technique is that the contralateral parotid gland can usually be completely excluded. However, achieving adequate coverage of the primary tumor can be challenging. On the other hand, the benefit of IMRT compared to traditional 3D-conformal RT is the ability to sculpt the dose around the target, sparing the surrounding critical organs as much as possible. While IMRT is superior to 3D-conformal RT regarding dose conformity and homogeneity, RT delivery time is generally increased, as is the number of monitor units, resulting in a greater integral body dose.

Summary

• Extent of soft palate or base of tongue invasion: The expert panel recommends ipsilateral radiation when there is <1cm of tumor invasion into the soft palate or base of tongue. If there is extension of 1 cm or greater, then the expert panel recommends bilateral neck irradiation because of the increased risk of occult contralateral nodal involvement.
• Nodal stage: For nodal stage of N2b or greater, the panel recommends bilateral neck irradiation, regardless of the extent of soft palate or base of tongue invasion. For nodal stage N0-1, the panel recommends basing the decision about whether to use ipsilateral or bilateral neck irradiation on the extent of soft palate and base of tongue invasion.
• HPV status: The panel concludes that there are insufficient data at this time to alter treatment decisions based on HPV status. The panel's recommendation is to treat with ipsilateral neck irradiation if the patient is an appropriate candidate based on the factors listed above, regardless of the patient's HPV status.

Abbreviations

• HPV, human papilloma virus
• SCCA, squamous cell carcinoma

Algorithms were not developed from criteria guidelines.

The recommendations are based on analysis of the current literature and expert panel consensus.

None stated

The American College of Radiology (ACR) Committee on Appropriateness Criteria and its expert panels have developed criteria for determining appropriate imaging examinations for diagnosis and treatment of specified medical condition(s). These criteria are intended to guide radiologists, radiation oncologists, and referring physicians in making decisions regarding radiologic imaging and treatment. Generally, the complexity and severity of a patient's clinical condition should dictate the selection of appropriate imaging procedures or treatments. Only those examinations generally used for evaluation of the patient's condition are ranked. Other imaging studies necessary to evaluate other co-existent diseases or other medical consequences of this condition are not considered in this document. The availability of equipment or personnel may influence the selection of appropriate imaging procedures or treatments. Imaging techniques classified as investigational by the U.S. Food and Drug Administration (FDA) have not been considered in developing these criteria; however, study of new equipment and applications should be encouraged. The ultimate decision regarding the appropriateness of any specific radiologic examination or treatment must be made by the referring physician and radiologist in light of all the circumstances presented in an individual examination.

An implementation strategy was not provided.

Not applicable: The guideline was not adapted from another source.

The American College of Radiology (ACR) provided the funding and the resources for these ACR Appropriateness Criteria®.

Committee on Appropriateness Criteria, Expert Panel on Radiation Oncology—Head & Neck Cancer

Panel Members: Anamaria Reyna Yeung, MD; Madhur Kumar Garg, MD; Jonathan J. Beitler, MD; Joshua Lawson, MD; Mark W. McDonald, MD; Harry Quon, MD, MS; John A. Ridge, MD, PhD; Nabil Saba, MD; Joseph K. Salama, MD; Richard V. Smith, MD; Sue S. Yom, MD, PhD

Not stated

This is the current release of the guideline.

Electronic copies: Available in Portable Document Format (PDF) from the American College of Radiology (ACR) Web site.

Print copies: Available from the American College of Radiology, 1891 Preston White Drive, Reston, VA 20191. Telephone: (703) 648-8900.

The following are available:

• ACR Appropriateness Criteria®. Overview. Reston (VA): American College of Radiology; 2 p. Electronic copies: Available in Portable Document Format (PDF) from the American College of Radiology (ACR) Web site .
• ACR Appropriateness Criteria®. Literature search process. Reston (VA): American College of Radiology; 1 p. Electronic copies: Available in PDF from the ACR Web site .
• ACR Appropriateness Criteria®. Evidence table development. Reston (VA): American College of Radiology; 4 p. Electronic copies: Available in PDF from the ACR Web site .

None available

This NGC summary was completed by ECRI Institute on February 7, 2012.

Instructions for downloading, use, and reproduction of the American College of Radiology (ACR) Appropriateness Criteria® may be found on the ACR Web site .