Effect of Radiotherapy Alone vs Radiotherapy With Concurrent Chemoradiotherapy on Survival Without Disease Relapse in Patients With Low-risk Nasopharyngeal Carcinoma

Abstract

IMPORTANCE Concurrent chemoradiotherapy has been the standard treatment for stage II nasopharyngeal carcinoma (NPC) based on data using 2-dimensional conventional radiotherapy. There is limited evidence for the role of chemotherapy with use of intensity-modulated radiation therapy (IMRT).OBJECTIVE To assess whether concurrent chemotherapy can be safely omitted for patients with low-risk stage II/T3N0 NPC treated with IMRT. DESIGN, SETTING, AND PARTICIPANTSThis multicenter, open-label, randomized, phase 3, noninferiority clinical trial was conducted at 5 Chinese hospitals, including 341 adult patients with low-risk NPC, defined as stage II/T3N0M0 without adverse features (all nodes <3 cm, no level IV/Vb nodes; no extranodal extension; Epstein-Barr virus DNA <4000 copies/mL), with enrollment between November 2015 and August 2020. The final date of follow-up was March 15, 2022.INTERVENTIONS Patients were randomly assigned to receive IMRT alone (n = 172) or concurrent chemoradiotherapy (IMRT with cisplatin, 100 mg/m 2 every 3 weeks for 3 cycles [n = 169]). MAIN OUTCOMES AND MEASURESThe primary end point was 3-year failure-free survival (time from randomization to any disease relapse or death), with a noninferiority margin of 10%. Secondary end points comprised overall survival, locoregional relapse-free survival, distant metastasis-free survival, adverse events, and health-related quality of life (QOL) measured by the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire (QLQ-C30; range, 0-100 points; minimum clinically important difference Ն10 for physical function, symptom control, or health-related QOL; higher score indicates better functioning and global health status or worse symptoms). RESULTS Among 341 randomized patients (mean [SD] age, 48 [10] years; 30% women), 334 (98.0%) completed the trial. Median follow-up was 46 months (IQR,. Three-year failure-free survival was 90.5% for the IMRT-alone group vs 91.9% for the concurrent chemoradiotherapy group (difference, −1.4%; 1-sided 95% CI, −7.4% to ϱ; P value for noninferiority, <.001). No significant differences were observed between groups in overall survival, locoregional relapse, or distant metastasis. The IMRT-alone group experienced a significantly lower incidence of grade 3 to 4 adverse events (17% vs 46%; difference, −29% [95% CI, −39% to −20%]), including hematologic toxicities (leukopenia, neutropenia) and nonhematologic toxicities (nausea, vomiting, anorexia, weight loss, mucositis). The IMRT-alone group had significantly better QOL scores during radiotherapy including the domains of global health status, social functioning, fatigue, nausea and vomiting, pain, insomnia, appetite loss, and constipation.CONCLUSIONS AND RELEVANCE Among patients with low-risk NPC, treatment with IMRT alone resulted in 3-year failure-free survival that was not inferior to concurrent chemoradiotherapy.

Long-term outcomes of nasopharyngeal carcinoma by Epstein-Barr virus status in the Chinese population: a multicenter investigation

“…Induction chemotherapy followed by chemoradiotherapy has become the main treatment methods and contributed to the improvements in treatment outcomes[8], The ve-year OS rate is 74%-88% [9][10][11]. However, the effect of radiotherapy alone was not inferior to concurrent chemoradiotherapy in patients with low-risk nasopharyngeal carcinoma [12]. In an international multicenter retrospective study [13], patients with NPC diagnosed between 2004 and 2017 in 36 hospitals in 11 countries were analyzed.…”

Treatment Considerations for Patients with Locoregionally Advanced Head and Neck Cancer with a Contraindication to Cisplatin

“…Even in highly selected patients who are deemed to have "low-risk" HNC, the incremental benefit of cisplatin over alternative systemic therapies and RT alone has been illustrated repeatedly [5][6][7][8]. One recent exception to this is in low-risk nasopharyngeal carcinoma, where treatment with intensity-modulated radiation therapy (IMRT) alone was not inferior to combined IMRT and cisplatin [9]. An in-depth review of treatment de-escalation studies is outside of the scope of this manuscript and has been reviewed elsewhere [10].…”

Radiotherapy Alone vs Radiotherapy With Concurrent Chemoradiotherapy and Survival of Patients With Low-Risk Nasopharyngeal Carcinoma

“…To the Editor The National Comprehensive Cancer Network (NCCN) guidelines currently recommend that concurrent chemoradiotherapy be the primary treatment for patients with T1-2N1M0, T3N0M0, and T2N0M0 NPC with high-risk features. A recent study reported that patients with low-risk stage II and T3N0M0 cancer who received IMRT alone had the same oncologic outcomes but better long-term quality of life than those who received concurrent chemoradiotherapy. We have 3 concerns about the definition of the truly low-risk NPC.…”

“…Prior evidence has shown that it is difficult to control tumors using IMRT alone or even with use of concurrent chemoradiotherapy if the primary tumor volume is very large . However, in this study, primary tumor volume was not taken into account when defining low-risk patients.…”