Efficacy
A search of the literature did not find level I, II or III-1 evidence to support this protocol. The expert reference panel supported publication of the protocol on the basis of the information summarised in the table below. The committee was most strongly influenced by Lee et al. 2009r and Xiao et al. 2009r.
Excellent treatment results have been obtained using standard radiation therapy alone in patients with stage I nasopharyngeal cancer (NPC). Excellent local and regional control rates have also been achieved using intensity-modulated radiation therapy (IMRT) whilst reducing late toxicities such as xerostomia. Lee et al. 2009 conducted a multi-institutional prospective trial using IMRT in patients with NPC and reported that outcome measure, local control and overall survival (OS), were maintained and the incidence of acute and late toxicities was reduced.r This study treated 68 patients with stage I to IVB nasopharyngeal carcinoma (Stage I n=9) with 70 Gy in 33 fractions (2.12 Gy/fx) to the primary tumour and 50.4-59.4 Gy in 33 fractions (1.5-1.8 Gy/fx) to areas at risk. For all stages the median follow up was 2.6 years, with estimated 2-year local progression-free (PF), regional PF, locoregional PF, and distant metastasis–free rates of 92.6%, 90.8%, 89.3%, and 84.7%, respectively. The estimated 2-year progression free and overall survivals were 72.7% and 80.2%, respectively. No T1 N0 patients experienced locoregional failure (LRF).
Xiao et al. 2009 analysed treatment outcomes for early stage NPC (T1-T2N0-N1M0) in 362 patients (T1N0M0 n=12) with a median follow up of 70 months.r Patients were treated using a conventionally fractionated (1.8–2 Gy per fraction and five daily fractions per week) 2D technique to a total dose of 64-80 Gy (median dose = 70 Gy) and 40–60 Gy (median dose = 52 Gy) to the node negative neck. After a median follow up of 70 months, of those with T1N0 disease, the 5-year overall survival rate and 5-year distant metastasis-free survival rate was 96.6% and 94.9%, respectively.
Figure 1. Overall survival (OS) curves for NPC patients with T1-2 N0-1 M0 receiving RT alone. Statistically significant difference found amongst OS rates of four groups compared using log-rank test.r
© Int J Radiat Oncol Biol Phys 2009r
Tang et al. 2022 randomised 341 patients with low risk stage II NPC (AJCC 7th edition) and T3N0 to IMRT alone or IMRT + concurrent chemotherapy.r Low risk were defined as all nodes < 3 cm, no level IV/Vb nodes, no extranodal extension and Epstein-Barr virus (EBV) DNA < 4000 copies/mL. Primary outcome was 3 year failure free survival (FFS) with a non inferiority margin of 10%. Authors reported that the 3 year FFS for IMRT alone (90.5%) was non inferior to concurrent CRT (91.9%) (p < 0.001). Secondary outcome of overall survival, loco-regional relapse free survival (LRRFS), and distant metastasis free survival (DMFS) was not significantly different between the two groups (refer Figure 2).
Figure 2. Failure-Free Survival According to Subgroupr
Figure legend: Failure-Free Survival According to Subgroup a Hazard ratios (HRs) and the associated 95% CIs were calculated using an unadjusted Cox proportional hazards model, which was also used to carry out the interaction test, incorporating the interaction term (eg, age × treatment), a covariate of interest (eg, sex), and the trial group. An HR of less than 1 indicated a decreased risk of failure-free survival after intensity-modulated radiation therapy alone compared with that after concurrent chemoradiotherapy.
b The index of Karnofsky performance scales is a primarily subjective score of physical ability used to assess the ability of a patient to carry on normal activities in life from normal health (100) to disabled (50) and death (0).
c According to the 7th edition TNM Staging System. ; T1: Nasopharynx, oropharynx or nasal cavity without parapharyngeal extension; T2: Parapharyngeal extension; T3: Bony structures of skull base and/or paranasal sinuses; N0: No regional lymph node metastasis; N1: Unilateral cervical, unilateral or bilateral retropharyngeal lymph nodes, above the supraclavicular fossa; ≤6 cm.
d Stage II includes T2N0 and the T1-2N1 subset; stage III includes T3N0 subset.
© Jama, 2022r
A meta-analysis by Liu et al. 2018 looked at the role of concurrent chemotherapy for Stage II NPC in the IMRT era.r A total of 7 studies were included. Comparing IMRT alone or IMRT plus concurrent chemotherapy. IMRT plus concurrent chemotherapy led to no survival benefit. Refer to Table 1 for the main characteristics of studies included. Results reported as OS (HR 1.17, 95% CI: 0.73–1.89, p = 0.508), progression free survival (PFS) (HR 0.76, 95% CI: 0.38–1.50, p = 0.430), DMFS (HR = 0.89, 95% CI: 0.33–2.41, p = 0.816), and LRRFS (HR 1.03, 95% CI: 0.95–1.12, p = 0.498). Concurrent chemoradiation therapy notably increased the risk of acute toxicities compared to IMRT alone.
Table 1. Studies included in meta-analysisr
© PLoS One, 2018r