Abstract
Purpose
To explore lymph node-related risk factors and investigate the benefit of different adjuvant therapy strategies in hypopharyngeal squamous-cell carcinoma (HPSCC) patients with nodal metastasis (N +).
Methods
We conducted a retrospective review covering 266 HPSCC patients with nodal metastasis. Kaplan–Meier curves and Cox proportional hazard models were utilized to evaluate recurrence-free survival (RFS) and independent risk factors.
Results
pT3-T4, extranodal extension, lymphovascular invasion, and lower lymph node involvement were high-risk factors leading to poorer RFS in N + HPSCC patients. Patients were classified into three groups based on the recursive-partitioning analysis (RPA). Postoperative chemoradiation significantly improved RFS in patients in the high-risk group (p < 0.001). For patients in the low- and intermediate-risk groups, the application of adjuvant therapies showed no significant benefit on RFS (p = 0.74 and 0.53, respectively).
Conclusions
The novel risk stratification for N + HPSCC patients can predict the risk of postoperative recurrence effectively. Adjuvant chemoradiation is preferred for patients in the high-risk group as it lowers risk of recurrence. Conversely, for patients in the low- and intermediate-risk groups, regular observation and follow-up strategies are a valid form of treatment.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
Availability of data and material
Research data are not shared.
References
American Joint Committee on Cancer (2017) AJCC Cancer Staging Manual, 8th edn. Springer, Cham
Ang KK, Trotti A, Brown BW et al (2001) Randomized trial addressing risk features and time factors of surgery plus radiotherapy in advanced head-and-neck cancer. Int J Radiat Oncol 51:571–578. https://doi.org/10.1016/s0360-3016(01)01690-x
Bernier J, Domenge C, Ozsahin M et al (2004) Postoperative Irradiation with or without Concomitant Chemotherapy for Locally Advanced Head and Neck Cancer. N Engl J Med 350:1945–1952. https://doi.org/10.1056/NEJMoa032641
Bray F, Ferlay J, Soerjomataram I et al (2018) Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin 68:394–424. https://doi.org/10.3322/caac.21492
Buckley JG, MacLennan K (2000) Cervical node metastases in laryngeal and hypopharyngeal cancer: A prospective analysis of prevalence and distribution. Head Neck 22:380–385. https://doi.org/10.1002/1097-0347(200007)22:4%3c380:AID-HED11%3e3.0.CO;2-E
Chung MJ, Kim YS, Kim JY et al (2016) Predictors of distant metastasis after radical surgery followed by postoperative radiotherapy with or without chemotherapy for oropharyngeal cancer. Cancer Res Treat 48:1167–1176. https://doi.org/10.4143/crt.2015.379
Cooper JS, Pajak TF, Forastiere AA et al (2004) Postoperative concurrent radiotherapy and chemotherapy for high-risk squamous-cell carcinoma of the head and neck. N Engl J Med 350:1937–1944. https://doi.org/10.1056/NEJMoa032646
Cooper JS, Zhang Q, Pajak TF et al (2012) Long-term follow-up of the RTOG 9501/intergroup phase III trial: postoperative concurrent radiation therapy and chemotherapy in high-risk squamous cell carcinoma of the head and neck. Int J Radiat Oncol 84:1198–1205. https://doi.org/10.1016/j.ijrobp.2012.05.008
Galiabovitch E, Hovens CM, Peters JS et al (2017) Routinely reported ‘equivocal’ lymphovascular invasion in prostatectomy specimens is associated with adverse outcomes. BJU Int 119:567–572. https://doi.org/10.1111/bju.13594
Goldenberg D, Mackley H, Koch W et al (2014) Age and stage as determinants of treatment for oral cavity and oropharyngeal cancers in the elderly. Oral Oncol 50:976–982. https://doi.org/10.1016/j.oraloncology.2014.07.008
Goto Y, Kodaira T, Furutani K et al (2013) Clinical outcome and patterns of recurrence of head and neck squamous cell carcinoma with a limited field of postoperative radiotherapy. Jpn J Clin Oncol 43:719–725. https://doi.org/10.1093/jjco/hyt066
Hall SF, Groome PA, Irish J, O’Sullivan B (2008) The natural history of patients with squamous cell carcinoma of the hypopharynx. Laryngoscope 118:1362–1371. https://doi.org/10.1097/MLG.0b013e318173dc4a
Heng Y, Zhu X, Zhou L et al (2020) The presence of risk factors and corresponding treatment strategies post-surgical resection in stage IV hypopharyngeal squamous cell carcinoma patients: a retrospective cohort study. Ann Transl Med 8(5):189. https://doi.org/10.21037/atm.2020.01.102
Ho AS, Kim S, Tighiouart M et al (2018) Association of quantitative metastatic lymph node burden with survival in hypopharyngeal and laryngeal cancer. JAMA Oncol 4:985. https://doi.org/10.1001/jamaoncol.2017.3852
Jones AS, Roland NJ, Field JK, Phillips DE (1994) The level of cervical lymph node metastases: their prognostic relevance and relationship with head and neck squamous carcinoma primary sites. Clin Otolaryngol 19:63–69. https://doi.org/10.1111/j.1365-2273.1994.tb01150.x
Kim DH, Kim WT, Lee JH et al (2015) Analysis of the prognostic factors for distant metastasis after induction chemotherapy followed by concurrent chemoradiotherapy for head and neck cancer. Cancer Res Treat 47:46–54. https://doi.org/10.4143/crt.2013.212
Koziol JA, Zhang J-Y, Casiano CA et al (2003) Recursive partitioning as an approach to selection of immune markers for tumor diagnosis. Clin Cancer Res 9:5120–5126
Layland MK, Sessions DG, Lenox J (2005) The influence of lymph node metastasis in the treatment of squamous cell carcinoma of the oral cavity, oropharynx, larynx, and hypopharynx: N0 versus N +. Laryngoscope 115:629–639. https://doi.org/10.1097/01.mlg.0000161338.54515.b1
Leemans CR, Tiwari R, Nauta JPJ et al (1993) Regional lymph node involvement and its significance in the development of distant metastases in head and neck carcinoma. Cancer 71:452–456. https://doi.org/10.1002/1097-0142(19930115)71:2%3c452:aid-cncr2820710228%3e3.0.co;2-b
Li G, Song H, Wang J et al (2016) Poor prognostic value of lymphovascular invasion for pT1 urothelial carcinoma with squamous differentiation in bladder cancer. Sci Rep 6:1–8. https://doi.org/10.1038/srep27586
Lin Z, Lin H, Lin C (2020) Dynamic prediction of cancer-specific survival for primary hypopharyngeal squamous cell carcinoma. Int J Clin Oncol 25:1260–1269. https://doi.org/10.1007/s10147-020-01671-4
Lydiatt WM, Patel SG, Sullivan B et al (2017) Head and neck cancers-major changes in the American Joint Committee on cancer eighth edition cancer staging manual. CA Cancer J Clin 67:122–137. https://doi.org/10.3322/caac.21389
Machtay M, Moughan J, Farach A et al (2012) Hypopharyngeal dose is associated with severe late toxicity in locally advanced head-and-neck cancer: an RTOG analysis. Int J Radiat Oncol Biol Phys 84:983–989. https://doi.org/10.1016/j.ijrobp.2012.03.005
Newman JR, Connolly TM, Illing EA et al (2015) Survival trends in Hypopharyngeal cancer: a population-based review. Laryngoscope 125:624–629. https://doi.org/10.1002/lary.24915
Putten L, Bree R, Doornaert PA et al (2015) Salvage surgery in post-chemoradiation laryngeal and hypopharyngeal carcinoma: outcome and review. Acta Otorhinolaryngol Ital 35:162–172
Ramnefjell M, Aamelfot C, Helgeland L, Akslen LA (2017) Vascular invasion is an adverse prognostic factor in resected non–small-cell lung cancer. APMIS 125:197–206. https://doi.org/10.1111/apm.12652
Saito Y, Omura G, Yasuhara K et al (2017) Prognostic value of lymphovascular invasion of the primary tumor in hypopharyngeal carcinoma after total laryngopharyngectomy. Head Neck 39:1535–1543. https://doi.org/10.1002/hed.24705
The National Comprehensive Cancer Network (2019) Head and Neck Cancers, Version 3. 2019, NCCN Clinical Practice Guidelines in Oncology. https://www.nccn.org/professionals/physician_gls/pdf/head-and-neck.pdf
Xing Y, Zhang J, Lin H et al (2016) Relation between the level of lymph node metastasis and survival in locally advanced head and neck squamous cell carcinoma. Cancer 122:534–545. https://doi.org/10.1002/cncr.29780
Funding
The study was supported by the Science and Technology Innovation Project of Shanghai Shen-kang Hospital Clinical Development Center under Grand (SHDC12015114); the Science and Technology Commission of Shanghai Municipality under Grand (16411950100); the National Natural Science Foundation of China under Grand (81772878, 30801283, 30972691); the Shanghai Science and Technology Development Funds under Grand (09QA1401000, 10QA1405900, 14411961900); the Training Program of the Excellent Young Talents of Shanghai Municipal Health System under Grand (XYQ2011055, XYQ2011015); and the Shanghai Municipal Science and Technology Foundation under Grand (11JC1410802).
Author information
Authors and Affiliations
Contributions
Study concepts: HQL, TW and LT. Study design: HQL, PYC and LT. Data acquisition: LZ, MZ and YS. Data analysis and interpretation: HQL, YH and XKZ. Statistical analysis: HQL and TW. Manuscript preparation: HQL, TW and LT. Manuscript editing: HQL, TW. Manuscript review: PYC, LT. All authors read and approved the final manuscript.
Corresponding authors
Ethics declarations
Conflict of interest
The authors declare that they have no competing interests.
Ethics approval
This study was approved by the Institutional Ethics Committee of the Eye & ENT Hospital of Fudan University.
Consent to participate
All participants gave informed consent to take part in the study.
Consent for publication
Not applicable.
Additional information
Publisher's Note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Electronic supplementary material
Below is the link to the electronic supplementary material.
Rights and permissions
About this article
Cite this article
Lin, H., Wang, T., Heng, Y. et al. Risk stratification of postoperative recurrence in hypopharyngeal squamous-cell carcinoma patients with nodal metastasis. J Cancer Res Clin Oncol 147, 803–811 (2021). https://doi.org/10.1007/s00432-020-03337-0
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00432-020-03337-0