Efficacy
Multiple randomised trials and meta-analyses which have demonstrated the superiority of concurrent chemoradiation (CRT) when compared to radiation therapy (RT) alone.r
The international standard schedule is 70Gy in 35 fractions with concurrent high-dose intermittent cisplatin for both HPV positive and HPV negative oropharyngeal squamous cell carcinoma (OPSCC).r
Radiation therapy plus cetuximab has been shown to be inferior compared to radiation therapy plus cisplatin in terms of overall survival and progression free survival.r Similar toxicity was noted between the two treatment arms.
Fractionation
Altered fractionation ± cetuximab is an alternative for patients not medically fit for concurrent chemotherapy.r
Human papillomavirus (HPV) status
The incidence of HPV related OPSCC is increasing. These patients have a different epidemiological profile to HPV unrelated head and neck SCC. HPV positive tumours carry a better prognosis than HPV negative tumours.rr This can be partially mitigated by their smoking history.r
Unilateral Treatment
Unilateral treatment may be appropriate for, but should be used selectively in patients with: (1) <1 cm extension of the tonsillar tumour onto either the soft palate or base of tongue; and/or (2) a single lymph node >3 cm but <6 cm, (AJCC 7th edition N2a)r or multiple small volume lymph nodes (AJCC 7th edition N2b)r. Except for the inclusion of N2b, this approach is endorsed by the ASTRO consensus guidelines.r
The decision of treating unilaterally should be made on anatomical staging and lateralisation, not on p16/HPV status.
In 2017 the Princess Margaret Hospital reported results of unilateral treatment in well lateralised tonsil tumours in the HPV era.r Unilateral treatment was administered to 102 patients, and HPV status was known in 96 patients (62 HPV positive , and 34 HPV negative). Eight N2b patients were treated unilaterally, and all had low volume disease (≤3 lymph node metastases). Two patients from the unilateral group received concurrent chemotherapy. Contralateral neck failure occurred in two patients, one HPV positive and one HPV negative, both were successfully salvaged.
Other series reported similarly low rates of contralateral neck failure.r A contemporary review of published studies reporting unilateral treatment outcomes for oropharyngeal cancers reports low rates of contralateral neck failure, although selection bias in the N2+ group is highly likely and should be interpreted with caution.r
A 2022 retrospective analysis conducted at a single institution, reported 9 (2%) of 403 T1-2, N0-N2b (AJCC 7th edition staged patients) who received unilateral radiation therapy experienced local recurrence, 13 (3%) neck recurrence, and 9 (2%) recurrence in the contralateral neck that had not received radiation.r The percentages of overall survival (OS) across five and ten years were 94% and 89%, respectively. The group was made up of 181 (45%) patients who had multiple involved nodes and 343 (85%) patients who had ipsilateral cervical nodal disease as evidenced by clinical and/or radiographic examination. Of the 301 tumours for which p16 testing was done, HPV was detected in 294 (73%).r
A January 2000 to May 2020 systemic literature review by the American Radium Society (ARS) provided evidence based recommendations for ipsilateral radiation for SCC of the tonsil in the setting of primary RT and postoperative adjuvant RT.r For primary RT they do not recommend ipsilateral therapy for patients with > 1 cm of tumour extension into the mucosa of the base of tongue and/or soft palate and recommend a high degree of caution in managing patients with multiple positive ipsilateral nodes. In terms of adjuvant chemo RT the committee advise against ipsilateral adjuvant radiation in pT1 patients if there was no clear documentation of detailed location of the primary site (and involvement of midline structures) before surgical resection, and caution against unilateral adjuvant RT for pT2 disease.r
A 2023 systematic review and meta-analysis objective was to determine the rate of nodal failure within the contralateral nonirradiated neck (CNF) following ipsilateral neck RT in patients with tonsil cancer.r Primary outcome was the pooled rate of CNF following ipsilateral neck RT. Secondary outcomes were the pooled rates of CNF by tumour and nodal staging categories from the 7th edition of the AJCC Cancer Staging Manual and rates of toxic effects. 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%). Patients with T3 to T4 tumours had a significantly higher rate of CNF than those with T1 to T2 tumours [11.5% (95% CI: 3.9%-19.1%) vs 1.8% (95% CI: 1.0%-2.6%), p < .001]. 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].
It should be noted most of the studies included in the analysis were retrospective in nature. It is important to exercise caution when interpreting these findings within the context of the more recent AJCC 8th edition staging system. In this updated system, HPV-associated OPSCC features distinct nodal staging compared to non-HPV associated disease, and the N2 designation now pertains to the presence of bilateral or contralateral lymph node involvement (formerly N2c in AJCC 7th edition). Additionally, certain clinically and prognostically significant risk factors, such as extranodal extension, could not be addressed due to limited available data.
Figure 1.0. Schematic diagram depicting “very-lateralised” tonsil primary suitable for consideration of ipsilateral radiation therapy.r
@ Int J Radiat Oncol Biol Phys, 2017r