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Background <p>The optimal treatment strategy for older patients with low-risk stage II or T3N0M0 nasopharyngeal carcinoma (NPC) remains undefined. This multicenter retrospective study compared the long-term outcomes and toxicities of intensity-modulated radiotherapy (IMRT) alone versus concurrent chemoradiotherapy with or without induction chemotherapy (CCRT ± IC) in this population, and explored the underlying tumor microenvironment (TME) characteristics.</p> Methods <p>A total of 1,265 older patients aged ≥ 60 years with low-risk NPC, defined as stage II or T3N0M0 disease without adverse features including lymph node diameter ≥ 3&#xa0;cm, extranodal extension, or EBV DNA ≥ 4000 copies/mL, were enrolled from three centers between 2010 and 2022. Propensity score matching (PSM) was used to balance baseline characteristics between treatment groups. Survival outcomes and toxicities were compared. Additionally, a deep learning-based Hover-Net model was applied to analyze immune cell infiltration in hematoxylin and eosin-stained sections from a subset of patients to investigate TME differences between risk groups.</p> Results <p>After PSM, IMRT alone demonstrated comparable survival outcomes to CCRT ± IC across all cohorts. In the training cohort, the 5-year cancer-specific survival rate was 91.4% in both groups (HR 1.07; <i>P</i> = 0.87), with consistent findings for progression-free survival, locoregional relapse-free survival, and distant metastasis-free survival. These results were validated in two external cohorts. However, CCRT ± IC led to significantly higher acute grade 3/4 hematologic and gastrointestinal toxicities. Hover-Net analysis revealed that the low-risk group exhibited significantly higher lymphocyte infiltration in the TME compared with the high-risk group (<i>P</i> &lt; 0.05), suggesting a potential biological basis for the favorable outcomes observed with IMRT alone.</p> Conclusions <p>For older patients with low-risk stage II or T3N0M0 NPC, IMRT alone achieves survival outcomes equivalent to CCRT ± IC with significantly fewer acute toxicities. The enriched lymphocyte infiltration in the low-risk TME provides a biological rationale for this chemotherapy-sparing approach, supporting IMRT alone as a preferred toxicity-de-escalation strategy.</p>

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Intensity-modulated radiotherapy alone versus concurrent chemoradiotherapy ± induction chemotherapy in older patients with low-risk stage II or T3N0M0 nasopharyngeal carcinoma

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年7月4日

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  • Zhi-Wei Liao,
  • Qizhen Xu,
  • Xue-Song Sun,
  • Chao Lin,
  • Hui-Tang Cai,
  • Liang Hu,
  • Qinghua Wang,
  • Yi-Bin Zhang,
  • Xiao-Long Chen,
  • Li-Jun Zhang,
  • Xiao-Dan Lin,
  • Yun-Hong Tian,
  • Hong-Wei Yu,
  • Yue-Feng Wen

摘要

Background

The optimal treatment strategy for older patients with low-risk stage II or T3N0M0 nasopharyngeal carcinoma (NPC) remains undefined. This multicenter retrospective study compared the long-term outcomes and toxicities of intensity-modulated radiotherapy (IMRT) alone versus concurrent chemoradiotherapy with or without induction chemotherapy (CCRT ± IC) in this population, and explored the underlying tumor microenvironment (TME) characteristics.

Methods

A total of 1,265 older patients aged ≥ 60 years with low-risk NPC, defined as stage II or T3N0M0 disease without adverse features including lymph node diameter ≥ 3 cm, extranodal extension, or EBV DNA ≥ 4000 copies/mL, were enrolled from three centers between 2010 and 2022. Propensity score matching (PSM) was used to balance baseline characteristics between treatment groups. Survival outcomes and toxicities were compared. Additionally, a deep learning-based Hover-Net model was applied to analyze immune cell infiltration in hematoxylin and eosin-stained sections from a subset of patients to investigate TME differences between risk groups.

Results

After PSM, IMRT alone demonstrated comparable survival outcomes to CCRT ± IC across all cohorts. In the training cohort, the 5-year cancer-specific survival rate was 91.4% in both groups (HR 1.07; P = 0.87), with consistent findings for progression-free survival, locoregional relapse-free survival, and distant metastasis-free survival. These results were validated in two external cohorts. However, CCRT ± IC led to significantly higher acute grade 3/4 hematologic and gastrointestinal toxicities. Hover-Net analysis revealed that the low-risk group exhibited significantly higher lymphocyte infiltration in the TME compared with the high-risk group (P < 0.05), suggesting a potential biological basis for the favorable outcomes observed with IMRT alone.

Conclusions

For older patients with low-risk stage II or T3N0M0 NPC, IMRT alone achieves survival outcomes equivalent to CCRT ± IC with significantly fewer acute toxicities. The enriched lymphocyte infiltration in the low-risk TME provides a biological rationale for this chemotherapy-sparing approach, supporting IMRT alone as a preferred toxicity-de-escalation strategy.