Ipsilateral Radiation for Squamous Cell Carcinoma of the Tonsil: Summary of Findings and Controversies from the ARS Appropriate Use Criteria Expert Panel on Tonsil Cancer

Background: In 2012 the American College of Radiology (ACR) published the Appropriateness Criteria for Ipsilateral Radiation for squamous cell carcinoma (SCC) of the tonsil. Since then there have been additional advancements and publications pertinent to this topic. Objectives: We performed an updated literature review and summarize the findings as well as potential controversies. Methods: We performed a PubMed search of articles published between January 2000 and June 2019 using various combinations of 25 pre-determined keywords and restricted to articles having the full text available, written in the English language, and on human subjects. Of the 46 citations returned from the search, the authors added 3 citations from bibliographies, websites or books not found in this literature search. Of the 49 citations, 30 citations were retained for further detailed review, and 14 of them were added to the evidence table. Articles were removed from the bibliography if they were not relevant or generalizable to the topic, focused on unknown primary disease, or they were no longer cited in the revised narrative text. Each study was graded using the Oxford Centre for Evidence-Based Medicine 2011 Levels of Evidence Table. Results: For clinically staged patients undergoing primary (chemo)radiotherapy, we identified 11 new articles published since the initial ACR guideline. Similar to the recommendation in the earlier guideline, unilateral radiotherapy was most often recommended for patients with tumors that were tonsil-confined or either \u3e 1 cm from midline or involving ≤ 1 cm of the mucosa of the base of tongue and/or soft palate. The published experiences demonstrated low rates of contralateral failure in both p16+ and p16- subsets. For patients undergoing primary tumor surgery and being considered for adjuvant radiotherapy, 3 new articles were identified. Multi-disciplinary evaluation is highly recommended before surgery or radiation, since surgical considerations for tonsil cancer may differ from those relevant to ipsilateral RT. The definitions of “well-lateralized” tonsil cancer from a surgical perspective could differ from that of a radiation oncologist. Consequently, whether all surgically resected T1-T2 tonsil SCC with a clinically node-negative contralateral neck are candidates for ipsilateral adjuvant RT warrants further discussion. Collectively among all of the literature reviewed, 1,031 patients were selected for either primary or adjuvant ipsilateral radiotherapy; 26 of 1,031 cases experienced contralateral disease progression. Of these, 19 were reported to have successful salvage and disease control at time of publication. Less than 1% (7 of 1,031) of patients managed unilaterally experienced contralateral progression that was not successfully salvaged. Other factors that might impact the selection for unilateral therapy but remain controversial include: patient age, performance status, number and size of ipsilateral nodes, number of involved ipsilateral nodal stations, clinical/pathological extranodal extension, and p16 status. Conclusions: This updated literature search provided additional information relevant to selection of patients for ipsilateral tonsil radiotherapy in the primary and adjuvant setting. Areas of controversies identified will require further reconciliation and investigation. Updated voting and committee recommendations will be presented

Ipsilateral Radiation for Squamous Cell Carcinoma of the Tonsil: Summary of Findings and Controversies from the ARS Appropriate Use Criteria Expert Panel on Tonsil Cancer

Background: In 2012 the American College of Radiology (ACR) published the Appropriateness Criteria for Ipsilateral Radiation for squamous cell carcinoma (SCC) of the tonsil. Since then there have been additional advancements and publications pertinent to this topic. Objectives: We performed an updated literature review and summarize the findings as well as potential controversies. Methods: We performed a PubMed search of articles published between January 2000 and June 2019 using various combinations of 25 pre-determined keywords and restricted to articles having the full text available, written in the English language, and on human subjects. Of the 46 citations returned from the search, the authors added 3 citations from bibliographies, websites or books not found in this literature search. Of the 49 citations, 30 citations were retained for further detailed review, and 14 of them were added to the evidence table. Articles were removed from the bibliography if they were not relevant or generalizable to the topic, focused on unknown primary disease, or they were no longer cited in the revised narrative text. Each study was graded using the Oxford Centre for Evidence-Based Medicine 2011 Levels of Evidence Table. Results: For clinically staged patients undergoing primary (chemo)radiotherapy, we identified 11 new articles published since the initial ACR guideline. Similar to the recommendation in the earlier guideline, unilateral radiotherapy was most often recommended for patients with tumors that were tonsil-confined or either \u3e 1 cm from midline or involving ≤ 1 cm of the mucosa of the base of tongue and/or soft palate. The published experiences demonstrated low rates of contralateral failure in both p16+ and p16- subsets. For patients undergoing primary tumor surgery and being considered for adjuvant radiotherapy, 3 new articles were identified. Multi-disciplinary evaluation is highly recommended before surgery or radiation, since surgical considerations for tonsil cancer may differ from those relevant to ipsilateral RT. The definitions of “well-lateralized” tonsil cancer from a surgical perspective could differ from that of a radiation oncologist. Consequently, whether all surgically resected T1-T2 tonsil SCC with a clinically node-negative contralateral neck are candidates for ipsilateral adjuvant RT warrants further discussion. Collectively among all of the literature reviewed, 1,031 patients were selected for either primary or adjuvant ipsilateral radiotherapy; 26 of 1,031 cases experienced contralateral disease progression. Of these, 19 were reported to have successful salvage and disease control at time of publication. Less than 1% (7 of 1,031) of patients managed unilaterally experienced contralateral progression that was not successfully salvaged. Other factors that might impact the selection for unilateral therapy but remain controversial include: patient age, performance status, number and size of ipsilateral nodes, number of involved ipsilateral nodal stations, clinical/pathological extranodal extension, and p16 status. Conclusions: This updated literature search provided additional information relevant to selection of patients for ipsilateral tonsil radiotherapy in the primary and adjuvant setting. Areas of controversies identified will require further reconciliation and investigation. Updated voting and committee recommendations will be presented

Postoperative Therapy for Resected Squamous Cell Carcinoma of the Head and Neck (SCCHN): Initial Findings of an American Radium Society (TM) (ARS) Appropriate Use Criteria Systematic Review (SR)

Background: Progress in SCCHN management requires re-evaluation of postoperative therapy for resected SCCHN. Since the ARS and American College of Radiology (ACR) published a literature review and expert consensus guideline on postoperative therapy in 2011, additional relevant clinical trials have been published. Objectives: To comprehensively evaluate existing prospective clinical studies of postoperative therapy for resected SCCHN using a formalized methodologic approach described by the Preferred Reporting Items for Systematic Review and Meta-Analyses (PRISMA) Protocol, and to identify areas of accepted recommendations, controversy and uncertainty. Methods: The methodologic protocol for this SR was guided by PRISMA. Ovid Medline and Embase were searched on 01/10/2019 using medical subject headings designed to capture all published studies of HN cancer and postoperative therapy. The PICO (participants, interventions, comparators, outcomes) framework was used to identify published randomized trials, single and multi-arm non-randomized prospective clinical trials, and SRs/meta-analyses that adhered to a published methodology. Longitudinal prospective cohort studies were included if there was a baseline pre-intervention assessment. Excluded studies had \u3c20 patients, were in non-English languages, or were case reports, case series, retrospective studies, large database studies, abstracts, preliminary analyses, narrative reviews, modeling studies, cell-line or non-clinical/non-human studies. Articles were selected if the population included adult patients with stage I-IVB SCCHN and no prior HN radiation who were treated with curative-intent surgery. Included disease sites were: oral cavity, oropharynx, hypopharynx, and larynx. The interventions of interest were postoperative radiation therapy (PORT), chemo-PORT, or postoperative chemotherapy, biologic therapy, targeted therapy, and/or immunotherapy. Studies were selected using Covidence ® software by two independent reviewers based on study relevance related to the inclusion/exclusion criteria. Each study was graded using the Oxford Centre for Evidence-Based Medicine 2011 Levels of Evidence Table. Results: A total of 5,689 studies were identified. After removal of duplicates, 5,660 studies were screened using the title and abstract, leading to 201 studies assessed for relevance using full-text review. After limitation to the eligibility criteria, 96 studies were identified. An additional 4 eligible studies were added that were published after the cut-off date or were not identified through the literature search. Studies with primary oncologic endpoints included 11 SRs, 24 randomized trials, 28 non-randomized trials, and 9 post-hoc analyses of randomized trials. Studies of non-oncologic endpoints included 2 SRs, 1 randomized trial, and 21 non-randomized clinical trials. Conclusions: This comprehensive, rigorously conducted SR identified 96 published prospective studies of postoperative therapy for SCCHN that constitute the evidence base for the ARS AUC HN Committee’s systematic review. Recommendations and identification of areas of continuing disagreement requiring further research will be generated from this evidence base; these will be described in more detail at the time of presentation

Ipsilateral radiation for squamous cell carcinoma of the tonsil: American Radium Society appropriate use criteria executive summary

BackgroundWe conducted the current systemic review to provide up-to-date literature summary and optimal evidence-based recommendations for ipsilateral radiation for squamous cell carcinoma of the tonsil.MethodsWe performed literature search of peer-reviewed journals through PubMed. The search strategy and subject-specific keywords were developed based on the expert panel's consensus. Articles published from January 2000 to May 2020 with full text available on PubMed and restricted to the English language and human subjects were included. Several prespecified search terms were used to identify relevant publications and additional evidence published since the initial American College of Radiology Appropriateness Criteria Ipsilateral Tonsil Radiation recommendation was finalized in 2012. The full bibliographies of identified articles were reviewed and irrelevant studies were removed.ResultsThe initial search and review returned 46 citations. The authors added three citations from bibliographies, websites, or books not found in the literature search. Of the 49 citations, 30 citations were retained for further detailed review, and 14 of them were added to the evidence table. Articles were removed from the bibliography if they were not relevant or generalizable to the topic, or focused on unknown primary disease. Several commonly encountered clinical case variants were created and panelists anonymously rated each treatment recommendation. The results were reviewed and disagreements discussed.ConclusionsThe panel provided updated evidence and recommendations for ipsilateral radiation for squamous cell carcinoma of the tonsil in the setting of primary radiation-based therapy and postoperative adjuvant radiotherapy. This committee did not reach agreements for some case variants due to a lack of strong evidence supporting specific treatment decisions, indicating a further need for research in these topics

Retreatment of Recurrent or Second Primary Head and Neck Cancer After Prior Radiation: Executive Summary of the American Radium Society® (ARS) Appropriate Use Criteria (AUC): Expert Panel on Radiation Oncology - Head and Neck Cancer

BACKGROUND: Re-treatment of recurrent or second primary head and neck cancers occurring in a previously irradiated field is complex. Few guidelines exist to support practice. METHODS: We performed an updated literature search of peer-reviewed journals in a systematic fashion. Search terms, key questions, and associated clinical case variants were formed by panel consensus. The literature search informed the committee during a blinded vote on the appropriateness of treatment options via the modified Delphi method. RESULTS: The final number of citations retained for review was 274. These informed five key questions, which focused on patient selection, adjuvant re-irradiation, definitive re-irradiation, stereotactic body radiation (SBRT), and re-irradiation to treat non-squamous cancer. Results of the consensus voting are presented along with discussion of the most current evidence. CONCLUSIONS: This provides updated evidence-based recommendations and guidelines for the re-treatment of recurrent or second primary cancer of the head and neck