Long-term results of elective mucosal irradiation for head and neck cancer of unknown primary in Chinese population: The EMICUP study

Shengjin Dou, Rongrong Li, Lin Zhang, Zhuoying Wang, Li Xie, Chenping Zhang, Guopei Zhu, Shengjin Dou, Rongrong Li, Lin Zhang, Zhuoying Wang, Li Xie, Chenping Zhang, Guopei Zhu

Abstract

Objective: Controversy still exists regarding the volume of radiation for head and neck cancer of unknown primary (HNCUP). Theoretically, elective mucosal irradiation (EMI) should achieve a balance between survival and toxicity. This prospective study was conducted to evaluate the long-term benefit of EMI in Chinese HNCUP patients.

Methods: A phase II, single-arm trial was performed at two centers in China. HNCUP patients with pathologically confirmed metastatic squamous cell carcinoma or poorly differentiated carcinoma were enrolled. Patients with metastatic lymph nodes limited to level IV and/or the supraclavicular fossa were excluded. The EMI approach was specifically customized to Chinese patients by differentiating HNCUP as putative nasopharyngeal carcinoma (NPC) or non-putative NPC. The primary endpoint was 3-year mucosal recurrence-free survival (MRFS).

Results: A total of 48 patients were enrolled between 02/02/2010 and 08/01/2018; 46 patients were analyzed, including 24 putative NPC and 22 non-putative NPC patients. No primary recurrence was observed during a median follow-up period of 70 months, and only 1 patient experienced out of field recurrence in the contralateral neck. The 3-year MRFS was 90.6% (95%CI: 76.4%-96.4%). The 5-year MRFS, regional-recurrence free survival (RRFS) and overall survival (OS) were 90.6% (95%CI: 76.4%-96.4%), 86.0% (95%CI: 71.1%-93.7%), and 90.6% (95%CI: 76.4%-96.4%), respectively. No grade 4 acute or late toxicities occurred, and the most frequent grade 3 acute toxicity was oral mucositis (45.7%).

Conclusion: To the best of our knowledge, this is the first prospective study to evaluate the long-term outcomes of EMI in Chinese HNCUP patients. Excellent MRFS and OS rates were observed. Further randomized studies are warranted.

Trial registration: ClinicalTrials.gov NCT02764216.

Keywords: head and neck; intensity-modulated radiation therapy; lymph node metastasis; mucosal irradiation; radiotherapy; unknown primary.

Conflict of interest statement

The authors declare that they have no competing interests.

© 2020 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.

Figures

Figure 1
Figure 1
Treatment principle of the how to deliver EMI approach for putative NPC and non‐putative NPC patients. Notes: *pathologically confirmed squamous cell carcinoma and poorly differentiated epithelial tumors; **radiology evaluation with enhanced MRI or CT; ***EBV VCA‐IgA or EBV DNA (preferred). Abbreviations: CCT, concurrent chemoradiotherapy; EBER, EBV‐encoded RNA; EBV, Epstein‐Barr virus; EMI, elective mucosal irradiation; HNCUP, head and neck cancer of unknown primary; HPV, human papillomavirus; IC, induction chemotherapy; LN, lymph node; ND, neck dissection; NPC, nasopharyngeal carcinoma; RPN, retropharyngeal node; RT, radiotherapy
Figure 2
Figure 2
Target volume delineation standard for non‐NPC patients (planning target volume for elective mucosal irradiation). The target volume including the unilateral half of the oropharynx, the hypopharynx, the supraglottic structures and neck LN levels irradiation (unilateral neck irradiation was performed for N1, N2a disease

Figure 3

Kaplan‐Meier survivals of all HNCUP…

Figure 3

Kaplan‐Meier survivals of all HNCUP patients. (A) MRFC, RRFS and DMFS curves of…

Figure 3
Kaplan‐Meier survivals of all HNCUP patients. (A) MRFC, RRFS and DMFS curves of all patients; (B): DFS and OS curves of all patients. Abbreviations: DFS, disease‐free survival; DMFS, distant metastasis‐free survival; MRFS, mucosal recurrence‐free survival; OS, overall survival; RRFS, regional recurrence‐free survival
Figure 3
Figure 3
Kaplan‐Meier survivals of all HNCUP patients. (A) MRFC, RRFS and DMFS curves of all patients; (B): DFS and OS curves of all patients. Abbreviations: DFS, disease‐free survival; DMFS, distant metastasis‐free survival; MRFS, mucosal recurrence‐free survival; OS, overall survival; RRFS, regional recurrence‐free survival

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