# Optimal timing of surgery in head and neck squamous cell carcinoma after neoadjuvant immunochemotherapy

**Authors:** Hanbo Seng, Yunli Fan, Rui Zhao, Yanyan Liu, Jinping Meng, Ziqi Wang, Yanyan Chen, Shengli Shao, Dongjie Seng

PMC · DOI: 10.3389/fonc.2026.1742883 · Frontiers in Oncology · 2026-02-06

## TL;DR

This study finds that waiting more than 3 weeks after cancer treatment before surgery reduces the effectiveness of treatment and increases complications in head and neck cancer patients.

## Contribution

The study identifies an optimal 3-week window between treatment and surgery for better outcomes in head and neck cancer patients.

## Key findings

- Waiting more than 3 weeks after treatment reduces tumor regression by 16-21%.
- Surgery after 3 weeks increases surgical complications and recurrence risks.
- Shorter intervals (under 3 weeks) are linked to better disease-free survival.

## Abstract

Our goal was to evaluate the influence of the interlude between neoadjuvant immunochemotherapy (NAIC) and surgery on both pathologic responses and surgical outcomes in head and neck squamous cell carcinoma (HNSCC).

Patients undergoing surgery for HNSCC following NAIC were retrospectively enrolled and determined based on the time to surgery (TTS). Impact of TTS on major pathologic response (mPR), pathologic complete response (pCR), surgical complication and 3-year disease free survival (DFS) was evaluated.

A total of 356 patients were enrolled. 225 patients (63.2%) achieved a mPR, among whom a pCR was achieved in 104 patients (29.2%). When compared to the TTS<1 week group, patients with a TTS of 1-2 weeks and those with a TTS of 2-3 weeks exhibited comparable rates of pCR and mPR achievement; however, patients who underwent surgery more than 3 weeks after the completion of NAIC had a significantly reduced likelihood of achieving total tumor regression by 16% (95% CI: 1%-23%) and lower probability of major tumor regression by 21% (95% CI: 5%-36%). The TTS >3 weeks group bore an additional 0.67-fold risk of experiencing surgical complications and 1.23-fold increased risk of adverse recurrence or death events compared to TTS <1 cohort.

A TTS exceeding 3 weeks was independently associated with a diminished likelihood of achieving both pCR and mPR, an increased rate of surgical complications, and a shorter duration of DFS. These findings suggest that the interval between surgery and the completion of NAIC may be optimal when kept within 3 weeks in HNSCC, though this warrants prospective validation.

## Linked entities

- **Diseases:** head and neck squamous cell carcinoma (MONDO:0010150), cancer (MONDO:0004992)

## Full-text entities

- **Genes:** CDKN2A (cyclin dependent kinase inhibitor 2A) [NCBI Gene 1029] {aka ARF, CAI2, CDK4I, CDKN2, CMM2, INK4}, CD274 (CD274 molecule) [NCBI Gene 29126] {aka ADMIO5, B7-H, B7H1, PD-L1, PDCD1L1, PDCD1LG1}
- **Diseases:** esophageal squamous cell carcinoma (MESH:D000077277), blood loss (MESH:D016063), Solid Tumors (MESH:D009369), dehiscence (MESH:D013529), wound (MESH:D014947), Complications (MESH:D008107), inflammatory (MESH:D007249), HNSCC (MESH:D000077195), non-small cell carcinoma (MESH:D002289), nodal (MESH:D013611), infections (MESH:D007239), stage III disease (MESH:D007676), death (MESH:D003643), metastasis (MESH:D009362), necrosis (MESH:D009336), chylous fistula (MESH:D002915), fistula (MESH:D005402), esophageal cancer (MESH:D004938), pCR (MESH:D005598), lymph node metastasis (MESH:D008207)
- **Chemicals:** platinum (MESH:D010984), pembrolizumab (MESH:C582435), NAIC (-), cisplatin (MESH:D002945), docetaxel (MESH:D000077143)
- **Species:** Homo sapiens (human, species) [taxon 9606]

## Full text

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## Figures

2 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12920233/full.md

## References

27 references — full list in the complete paper: https://tomesphere.com/paper/PMC12920233/full.md

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Source: https://tomesphere.com/paper/PMC12920233