Association of Unilateral Radiotherapy With Contralateral Lymph Node Failure Among Patients With Squamous Cell Carcinoma of the Tonsil

Abstract

ImportanceIpsilateral 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]).ObjectiveTo determine the rate of CNF following ipsilateral neck RT in patients with tonsil cancer.Data SourcesDatabases 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.Study SelectionStudies 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.Data Extraction and SynthesisData 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.Main Outcomes and MeasuresPrimary 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 and rates of toxic effects.ResultsA 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, −7.8% 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 < .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 = .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 = .04). The crude rates of xerostomia of grade 3 or greater and feeding tube use were 0.9% (95% CI, –0.2% to 1.9%) and 13.3% (95% CI, 8.3%-18.3%), respectively.Conclusions and RelevanceIn 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.

Contralateral Neck Recurrence Rates After Ipsilateral Neck Adjuvant Radiation in Head and Neck Carcinomas with a Pathologically Negative Contralateral Neck

“…Second, to our knowledge, 11,12 this is just the second study 16 of ipsilateral neck RT to reference AJCC 8 th edition staging and the first to use it for an OPX cohort. The American Radium Society guideline comments, “The literature review performed for this guideline did not return any titles that used the AJCC 8 th edition staging system.” Perhaps for inability to separately evaluate HPV+ oropharynx nodal staging, the guideline “strongly recommends the use of bilateral neck irradiation as usually appropriate after neck dissection in cases of multiple pathologically positive ipsilateral lymph nodes and in the presence of macroscopic extranodal extension.” However, 29% of our p16+ OPX population had ≥ 2 pathologically positive nodes and 32% had ENE.…”

“…Second, to our knowledge, 11,12 this is just the second study 16 of ipsilateral neck RT to reference AJCC 8 th edition staging and the first to use it for an OPX cohort. The American Radium Society guideline comments, "The literature review performed for this guideline did not return any titles that used the AJCC 8 th edition staging system."…”

“…To frame these results, two recent meta-analyses of ipsilateral neck RT for tonsillar 11 and OC 12 cancers published by Razavian et al are instructive. In the first 11 – a meta-analysis of ipsilateral neck RT delivered to 1487 tonsillar cancer patients drawn from 17 studies – the pooled rate of contralateral neck recurrence was 1.9%.…”

“…To frame these results, two recent meta-analyses of ipsilateral neck RT for tonsillar 11 and OC 12 cancers published by Razavian et al are instructive. In the first 11 – a meta-analysis of ipsilateral neck RT delivered to 1487 tonsillar cancer patients drawn from 17 studies – the pooled rate of contralateral neck recurrence was 1.9%. Increasing T stages were associated with higher contralateral recurrence risk (up to 16% for T4 tumors) but increasing N stages (N2b – N3 vs. N0 – N2a) were not (3% vs. 1.7%, p = 0.07).…”

Current Status and Future Directions of Proton Therapy for Head and Neck Carcinoma

“…Unilateral neck irradiation is another de-escalation strategy that can reduce toxicity and improve QoL for selected patients with early-stage and lateralized OPC [ 71 , 72 , 73 ], and further unintended dose reduction in the contralateral neck can be achieved by taking advantage of the steep dose gradient of protons [ 74 , 75 ]. Recently, a multi-institutional prospective analysis conducted by the Proton Collaborative Group on patients with OPC subjected to ipsilateral PT reported an excellent contralateral neck failure rate, comparable to failure rates observed with photon RT [ 76 ].…”