{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,18]],"date-time":"2026-09-18T00:21:59Z","timestamp":1789690919552,"version":"4.0.1"},"reference-count":43,"publisher":"American Medical Association (AMA)","issue":"2","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JAMA Netw Open"],"abstract":"Importance<\/jats:title>Ipsilateral neck radiotherapy (RT) is controversial in some patients with tonsil cancer due to concern for nodal failure within the contralateral nonirradiated neck (hereinafter referred to as contralateral neck failure [CNF]).<\/jats:p><\/jats:sec>Objective<\/jats:title>To determine the rate of CNF following ipsilateral neck RT in patients with tonsil cancer.<\/jats:p><\/jats:sec>Data Sources<\/jats:title>Databases including PubMed, Embase, Web of Science, and Cochrane Library were queried for peer-reviewed, English language articles published between January 1, 1980, and December 31, 2021.<\/jats:p><\/jats:sec>Study Selection<\/jats:title>Studies reporting rates of CNF from at least 20 patients treated with ipsilateral neck RT. Studies were excluded if they lacked full text, reported results from databases or systematic reviews, or did not provide RT details.<\/jats:p><\/jats:sec>Data Extraction and Synthesis<\/jats:title>Data were extracted following the PRISMA reporting guideline. Study quality was assessed using criteria from a methodological index for nonrandomized studies. Pooled outcomes were estimated using random-effects models.<\/jats:p><\/jats:sec>Main Outcomes and Measures<\/jats:title>Primary outcome was the pooled rate of CNF following ipsilateral neck RT. Secondary outcomes were the pooled rates of CNF by tumor and nodal staging categories from the 7th edition of the AJCC Cancer Staging Manual<\/jats:italic> and rates of toxic effects.<\/jats:p><\/jats:sec>Results<\/jats:title>A total of 17 studies (16 retrospective and 1 prospective) including 1487 unique patients were identified. The pooled risk of CNF was 1.9% (95% CI, 1.2%-2.6%). The rate of CNF by tumor (T) category was as follows: 1.3% (95% CI, 0.3%-2.3%) for T1; 3.0% (95% CI, 1.6%-4.4%) for T2; 11.3% (95% CI, 3.3%-19.2%) for T3; and 16.0% (95% CI, \u22127.8% to 39.8%) for T4. Patients with T3 to T4 tumors had a significantly higher rate of CNF than those with T1 to T2 tumors (11.5% [95% CI, 3.9%-19.1%] vs 1.8% [95% CI, 1.0%-2.6%]; P<\/jats:italic>\u2009&amp;lt;\u2009.001). The rate of CNF by nodal (N) category was 1.2% (95% CI, 0.1%-2.2%) for N0; 4.8% (95% CI, 2.4%-7.2%) for N1; 3.1% (95% CI, 0.4%-5.8%) for N2a; 3.1% (95% CI, 1.2%-4.9%) for N2b; and 0 (95% CI, not applicable) for N3. Rates of CNF were similar for patients with N2b to N3 and N0 to N2a disease (3.0% [95% CI, 1.2%-4.7%] vs 1.7% [95% CI, 0.6%-2.8%], respectively; P<\/jats:italic>\u2009=\u2009.07). Compared with bilateral RT, ipsilateral RT was associated with increased risk of CNF (log odds ratio, 1.29 [95% CI, 0.09-2.48]; P<\/jats:italic>\u2009=\u2009.04). The crude rates of xerostomia of grade 3 or greater and feeding tube use were 0.9% (95% CI, \u20130.2% to 1.9%) and 13.3% (95% CI, 8.3%-18.3%), respectively.<\/jats:p><\/jats:sec>Conclusions and Relevance<\/jats:title>In this systematic review and meta-analysis, ipsilateral neck RT was associated with a low rate of CNF in patients with small, lateralized tonsil cancers. Bilateral neck RT was associated with lower risk of CNF compared with ipsilateral neck RT. Patients with tumors of a higher T category were at increased risk for CNF following ipsilateral neck RT, and advanced nodal stage was not associated with CNF. Rates of toxic effects appeared favorable in patients treated with ipsilateral neck RT.<\/jats:p><\/jats:sec>","DOI":"10.1001\/jamanetworkopen.2022.55209","type":"journal-article","created":{"date-parts":[[2023,2,8]],"date-time":"2023-02-08T16:04:57Z","timestamp":1675872297000},"page":"e2255209","source":"Crossref","is-referenced-by-count":12,"title":["Association of Unilateral Radiotherapy With Contralateral Lymph Node Failure Among Patients With Squamous Cell Carcinoma of the Tonsil"],"prefix":"10.1001","volume":"6","author":[{"given":"Niema B.","family":"Razavian","sequence":"first","affiliation":[{"name":"Department of Radiation Oncology, Wake Forest University School of Medicine, Winston-Salem, North Carolina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"suffix":"Jr","given":"Ralph B.","family":"D\u2019Agostino","sequence":"additional","affiliation":[{"name":"Department of Biostatistics and Data Science, Wake Forest University School of Medicine, Winston-Salem, North Carolina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cole R.","family":"Steber","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology, Wake Forest University School of Medicine, Winston-Salem, North Carolina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Corbin A.","family":"Helis","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology, Fort Belvoir Community Hospital, Fort Belvoir, Virginia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ryan T.","family":"Hughes","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology, Wake Forest University School of Medicine, Winston-Salem, North Carolina"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"10","published-online":{"date-parts":[[2023,2,8]]},"reference":[{"issue":"3","key":"zoi221566r1","doi-asserted-by":"publisher","first-page":"290","DOI":"10.1097\/01.coc.0000209510.19360.f9","article-title":"Definitive radiotherapy for tonsillar squamous cell carcinoma.","volume":"29","author":"Mendenhall","year":"2006","journal-title":"Am J Clin Oncol"},{"issue":"4","key":"zoi221566r2","doi-asserted-by":"publisher","first-page":"265","DOI":"10.1016\/0167-8140(89)90138-2","article-title":"A multivariate primary tumour control analysis in 465 patients treated by radical radiotherapy for cancer of the tonsillar region: clinical and treatment parameters as prognostic factors.","volume":"14","author":"Bataini","year":"1989","journal-title":"Radiother Oncol"},{"issue":"34","key":"zoi221566r3","doi-asserted-by":"publisher","first-page":"3858","DOI":"10.1200\/JCO.2014.55.3925","article-title":"Randomized phase III trial to test accelerated versus standard fractionation in combination with concurrent cisplatin for head and neck carcinomas in the Radiation Therapy Oncology Group 0129 trial: long-term report of efficacy and toxicity.","volume":"32","author":"Nguyen-Tan","year":"2014","journal-title":"J Clin Oncol"},{"issue":"5","key":"zoi221566r4","doi-asserted-by":"publisher","first-page":"1002","DOI":"10.1016\/j.ijrobp.2017.02.218","article-title":"Final report of a prospective randomized trial to evaluate the dose-response relationship for postoperative radiation therapy and pathologic risk groups in patients with head and neck cancer.","volume":"98","author":"Rosenthal","year":"2017","journal-title":"Int J Radiat Oncol Biol Phys"},{"issue":"9","key":"zoi221566r6","doi-asserted-by":"publisher","first-page":"2807","DOI":"10.1002\/hed.v43.9","article-title":"Unilateral versus bilateral nodal irradiation: current evidence in the treatment of squamous cell carcinoma of the head and neck.","volume":"43","author":"Nuyts","year":"2021","journal-title":"Head Neck"},{"issue":"2","key":"zoi221566r7","doi-asserted-by":"publisher","first-page":"456","DOI":"10.1016\/j.ijrobp.2021.05.114","article-title":"Patient-reported toxicity and quality-of-life profiles in patients with head and neck cancer treated with definitive radiation therapy or chemoradiation.","volume":"111","author":"Van den Bosch","year":"2021","journal-title":"Int J Radiat Oncol Biol Phys"},{"issue":"1","key":"zoi221566r8","doi-asserted-by":"publisher","first-page":"83","DOI":"10.1016\/j.radonc.2007.03.002","article-title":"Unilateral versus bilateral irradiation in squamous cell head and neck cancer in relation to patient-rated xerostomia and sticky saliva.","volume":"85","author":"Jellema","year":"2007","journal-title":"Radiother Oncol"},{"issue":"3","key":"zoi221566r9","doi-asserted-by":"publisher","first-page":"695","DOI":"10.1016\/S0360-3016(01)01512-7","article-title":"Xerostomia and its predictors following parotid-sparing irradiation of head-and-neck cancer.","volume":"50","author":"Eisbruch","year":"2001","journal-title":"Int J Radiat Oncol Biol Phys"},{"issue":"1","key":"zoi221566r10","doi-asserted-by":"publisher","first-page":"17","DOI":"10.1002\/hed.v39.1","article-title":"Unilateral radiotherapy for surgically resected lateralized squamous cell carcinoma of the tonsil.","volume":"39","author":"Rackley","year":"2017","journal-title":"Head Neck"},{"issue":"1","key":"zoi221566r11","doi-asserted-by":"publisher","first-page":"204","DOI":"10.1016\/j.ijrobp.2011.06.1975","article-title":"Unilateral radiotherapy for the treatment of tonsil cancer.","volume":"83","author":"Chronowski","year":"2012","journal-title":"Int J Radiat Oncol Biol Phys"},{"issue":"1","key":"zoi221566r12","doi-asserted-by":"publisher","first-page":"7","DOI":"10.1016\/j.ijrobp.2012.03.049","article-title":"In regard to Chronowski et al.","volume":"85","author":"Geropantas","year":"2013","journal-title":"Int J Radiat Oncol Biol Phys"},{"issue":"3","key":"zoi221566r13","doi-asserted-by":"publisher","first-page":"682","DOI":"10.1016\/j.ijrobp.2009.08.042","article-title":"Ipsilateral irradiation for oral and oropharyngeal carcinoma treated with primary surgery and postoperative radiotherapy.","volume":"78","author":"Vergeer","year":"2010","journal-title":"Int J Radiat Oncol Biol Phys"},{"issue":"5","key":"zoi221566r14","doi-asserted-by":"publisher","first-page":"1365","DOI":"10.1016\/j.ijrobp.2008.10.023","article-title":"Freedom from local and regional failure of contralateral neck with ipsilateral neck radiotherapy for node-positive tonsil cancer: results of a prospective management approach.","volume":"74","author":"Rusthoven","year":"2009","journal-title":"Int J Radiat Oncol Biol Phys"},{"issue":"8","key":"zoi221566r15","doi-asserted-by":"publisher","first-page":"1647","DOI":"10.1002\/hed.v39.8","article-title":"Low rates of contralateral neck failure in unilaterally treated oropharyngeal squamous cell carcinoma with prospectively defined criteria of lateralization.","volume":"39","author":"Hu","year":"2017","journal-title":"Head Neck"},{"issue":"1","key":"zoi221566r16","doi-asserted-by":"publisher","first-page":"392","DOI":"10.1002\/hed.v43.1","article-title":"Ipsilateral radiation for squamous cell carcinoma of the tonsil: American Radium Society appropriate use criteria executive summary.","volume":"43","author":"Tsai","year":"2021","journal-title":"Head Neck"},{"issue":"5","key":"zoi221566r17","doi-asserted-by":"publisher","first-page":"613","DOI":"10.1002\/hed.21993","article-title":"ACR Appropriateness Criteria ipsilateral radiation for squamous cell carcinoma of the tonsil.","volume":"34","author":"Yeung","year":"2012","journal-title":"Head Neck"},{"issue":"9","key":"zoi221566r18","doi-asserted-by":"publisher","first-page":"1299","DOI":"10.1002\/hed.v38.9","article-title":"ACR Appropriateness Criteria locoregional therapy for resectable oropharyngeal squamous cell carcinomas.","volume":"38","author":"Beitler","year":"2016","journal-title":"Head Neck"},{"issue":"160","key":"zoi221566r19","doi-asserted-by":"publisher","first-page":"n160","DOI":"10.1136\/bmj.n160","article-title":"PRISMA 2020 explanation and elaboration: updated guidance and exemplars for reporting systematic reviews.","volume":"372","author":"Page","year":"2021","journal-title":"BMJ"},{"issue":"9","key":"zoi221566r20","doi-asserted-by":"publisher","first-page":"712","DOI":"10.1046\/j.1445-2197.2003.02748.x","article-title":"Methodological index for non-randomized studies (MINORS): development and validation of a new instrument.","volume":"73","author":"Slim","year":"2003","journal-title":"ANZ J Surg"},{"issue":"1","key":"zoi221566r22","doi-asserted-by":"publisher","first-page":"69","DOI":"10.1016\/j.radonc.2012.12.006","article-title":"Unilateral neck irradiation for well-lateralized oropharyngeal cancer.","volume":"106","author":"Al-Mamgani","year":"2013","journal-title":"Radiother Oncol"},{"issue":"23","key":"zoi221566r23","doi-asserted-by":"publisher","first-page":"4594","DOI":"10.1002\/cncr.v123.23","article-title":"Comparison of unilateral versus bilateral intensity-modulated radiotherapy for surgically treated squamous cell carcinoma of the palatine tonsil.","volume":"123","author":"Chin","year":"2017","journal-title":"Cancer"},{"issue":"6","key":"zoi221566r24","doi-asserted-by":"publisher","first-page":"616","DOI":"10.1016\/j.oraloncology.2015.03.013","article-title":"Freedom from local and regional failure of contralateral neck with ipsilateral neck radiotherapy for node-positive tonsil cancer: updated results of an institutional clinical management approach.","volume":"51","author":"Dan","year":"2015","journal-title":"Oral Oncol"},{"key":"zoi221566r25","doi-asserted-by":"publisher","first-page":"35","DOI":"10.1016\/j.oraloncology.2017.10.010","article-title":"Risk of contralateral nodal failure following ipsilateral IMRT for node-positive tonsillar cancer.","volume":"75","author":"Gottumukkala","year":"2017","journal-title":"Oral Oncol"},{"issue":"1","key":"zoi221566r26","doi-asserted-by":"publisher","first-page":"159","DOI":"10.1016\/j.ijrobp.2017.01.018","article-title":"Re-evaluation of ipsilateral radiation for T1-T2N0-N2b tonsil carcinoma at the Princess Margaret Hospital in the human papillomavirus era, 25 years later.","volume":"98","author":"Huang","year":"2017","journal-title":"Int J Radiat Oncol Biol Phys"},{"issue":"2","key":"zoi221566r27","doi-asserted-by":"publisher","first-page":"123","DOI":"10.1016\/S0167-8140(99)00051-1","article-title":"Cancer of the tonsil: the results of ipsilateral radiation treatment.","volume":"51","author":"Jackson","year":"1999","journal-title":"Radiother Oncol"},{"issue":"8","key":"zoi221566r28","doi-asserted-by":"publisher","first-page":"2151","DOI":"10.1007\/s00405-015-3725-3","article-title":"Ipsilateral radiotherapy for squamous cell carcinoma of the tonsil.","volume":"273","author":"Kennedy","year":"2016","journal-title":"Eur Arch Otorhinolaryngol"},{"issue":"4","key":"zoi221566r29","doi-asserted-by":"publisher","first-page":"1097","DOI":"10.4143\/crt.2016.425","article-title":"Comparison of the clinical outcomes of patients with squamous cell carcinoma of the tonsil receiving postoperative ipsilateral versus bilateral neck radiotherapy: a propensity score matching analysis (KROG 11-07).","volume":"49","author":"Kim","year":"2017","journal-title":"Cancer Res Treat"},{"issue":"3","key":"zoi221566r30","doi-asserted-by":"publisher","first-page":"317","DOI":"10.1002\/hed.v36.3","article-title":"Tonsillar cancer: the Peter MacCallum experience with unilateral and bilateral irradiation.","volume":"36","author":"Liu","year":"2014","journal-title":"Head Neck"},{"issue":"9","key":"zoi221566r31","doi-asserted-by":"publisher","first-page":"901","DOI":"10.1016\/j.oraloncology.2014.06.019","article-title":"Multiple cervical lymph node involvement and extra-capsular extension predict for contralateral nodal recurrence after ipsilateral radiotherapy for squamous cell carcinoma of the tonsil.","volume":"50","author":"Lynch","year":"2014","journal-title":"Oral Oncol"},{"issue":"9","key":"zoi221566r32","doi-asserted-by":"publisher","first-page":"2937","DOI":"10.1002\/hed.v41.9","article-title":"Ipsilateral neck radiotherapy in N2b well-lateralized tonsil cancer\u2014approach with caution.","volume":"41","author":"Maskell","year":"2019","journal-title":"Head Neck"},{"issue":"1","key":"zoi221566r33","doi-asserted-by":"publisher","first-page":"91","DOI":"10.1016\/0360-3016(80)90209-6","article-title":"Is contralateral neck treatment necessary in early carcinoma of the tonsil?","volume":"6","author":"Murthy","year":"1980","journal-title":"Int J Radiat Oncol Biol Phys"},{"issue":"2","key":"zoi221566r34","doi-asserted-by":"publisher","first-page":"332","DOI":"10.1016\/S0360-3016(01)01613-3","article-title":"The benefits and pitfalls of ipsilateral radiotherapy in carcinoma of the tonsillar region.","volume":"51","author":"O\u2019Sullivan","year":"2001","journal-title":"Int J Radiat Oncol Biol Phys"},{"issue":"9","key":"zoi221566r35","doi-asserted-by":"publisher","DOI":"10.7759\/cureus.322","article-title":"Patterns of relapse in squamous cell carcinoma of the tonsil\u2014unilateral vs bilateral radiation in the HPV-era.","volume":"7","author":"Ye","year":"2015","journal-title":"Cureus"},{"issue":"4","key":"zoi221566r36","doi-asserted-by":"publisher","first-page":"479","DOI":"10.1016\/S1470-2045(22)00058-4","article-title":"Elective upper-neck versus whole-neck irradiation of the uninvolved neck in patients with nasopharyngeal carcinoma: an open-label, non-inferiority, multicentre, randomised phase 3 trial.","volume":"23","author":"Tang","year":"2022","journal-title":"Lancet Oncol"},{"issue":"1","key":"zoi221566r37","doi-asserted-by":"publisher","first-page":"196","DOI":"10.1186\/s13014-020-01636-x","article-title":"Preservation of swallowing in resected oral cavity squamous cell carcinoma: examining radiation volume effects (PRESERVE): study protocol for a randomized phase II trial.","volume":"15","author":"Lang","year":"2020","journal-title":"Radiat Oncol"},{"key":"zoi221566r38","doi-asserted-by":"publisher","DOI":"10.1016\/j.oraloncology.2020.105165","article-title":"Comparing unilateral vs bilateral neck management in lateralized oropharyngeal cancer between surgical and radiation oncologists: an international practice pattern survey.","volume":"114","author":"de Almeida","year":"2021","journal-title":"Oral Oncol"},{"issue":"9","key":"zoi221566r39","doi-asserted-by":"publisher","first-page":"956","DOI":"10.1200\/JCO.20.03128","article-title":"Reduced-dose radiation therapy for HPV-associated oropharyngeal carcinoma (NRG Oncology HN002).","volume":"39","author":"Yom","year":"2021","journal-title":"J Clin Oncol"},{"issue":"2","key":"zoi221566r40","doi-asserted-by":"publisher","first-page":"297","DOI":"10.1093\/annonc\/mdy522","article-title":"OPTIMA: a phase II dose and volume de-escalation trial for human papillomavirus-positive oropharyngeal cancer.","volume":"30","author":"Seiwert","year":"2019","journal-title":"Ann Oncol"},{"issue":"1","key":"zoi221566r42","doi-asserted-by":"publisher","first-page":"8","DOI":"10.1016\/j.ijrobp.2012.09.017","article-title":"In Reply to Geropantas et al.","volume":"85","author":"Chronowski","year":"2013","journal-title":"Int J Radiat Oncol Biol Phys"},{"issue":"5","key":"zoi221566r43","doi-asserted-by":"publisher","first-page":"1396","DOI":"10.1016\/j.ijrobp.2017.12.228","article-title":"Functional swallowing outcomes using FEES evaluation after swallowing-sparing IMRT in unilateral versus bilateral neck radiation.","volume":"100","author":"Tam","year":"2018","journal-title":"Int J Radiat Oncol Biol Phys"},{"key":"zoi221566r41","volume-title":"American Joint Committee on Cancer: AJCC Cancer Staging Manual","author":"Amin","year":"2018","edition":"8th ed"},{"key":"zoi221566r5","unstructured":"National Comprehensive Cancer Network. Head and neck cancers (version 1.2022). Accessed April 15, 2022. https:\/\/www.nccn.org\/professionals\/physician_gls\/pdf\/head-and-neck.pdf"},{"key":"zoi221566r21","unstructured":"R Foundation for Statistical Computing. A language and environment for statistical computing. Accessed August 26, 2022. https:\/\/www.R-project.org\/"}],"container-title":["JAMA Network Open"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/jamanetwork.com\/journals\/jamanetworkopen\/articlepdf\/2801100\/razavian_2023_oi_221566_1675111554.13264.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,2,8]],"date-time":"2023-02-08T16:05:01Z","timestamp":1675872301000},"score":1,"resource":{"primary":{"URL":"https:\/\/jamanetwork.com\/journals\/jamanetworkopen\/fullarticle\/2801100"}},"subtitle":["A Systematic Review and Meta-analysis"],"short-title":[],"issued":{"date-parts":[[2023,2,8]]},"references-count":43,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2023,2,1]]}},"URL":"https:\/\/doi.org\/10.1001\/jamanetworkopen.2022.55209","relation":{},"ISSN":["2574-3805"],"issn-type":[{"value":"2574-3805","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,2,8]]}}}