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Metastatic lymph node burden predictive of survival in patients undergoing primary surgery for laryngeal and hypopharyngeal cancer

  • Original Article – Clinical Oncology
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Abstract

Purpose

Metastatic lymph node (LN) burden is one of the most important prognosticators in human solid cancers, but has rarely been examined in laryngeal and hypopharyngeal cancers (LHC). We evaluated the nodal factors predictive of recurrence and survival in patients with LHC.

Methods

This study included 141 consecutive patients who underwent primary surgery and neck dissection for previously untreated LHC at our tertiary referral centre. Nodal factors included the presence of pathological LN metastasis, number of positive LNs, LN ratio, and extra-nodal extension (ENE). Our proposed N classification was analysed by recursive partitioning analysis and compared with the AJCC and other N classifications using the c-index. Univariate and multivariate Cox proportional hazard regression analyses were used to define significant predictors of post-treatment disease-free survival (DFS) and overall survival (OS).

Results

Of the 141 patients, 66 (46.8%) had positive LNs, and 27 (19.1%) had ENE. In multivariate analyses, the number of positive LNs was strongly associated with DFS and OS outcomes (P < 0.01). Our new N classification was proposed with four categories, such as N0 (0 LN +), N1 (1 LN +), N2 (2–4 LN + or ENE) and N3 (≥ 5 LN +). The C-index of our new N classification improved the OS prediction (0.718) compared with the AJCC and the other N classifications (0.704–0.713).

Conclusion

Metastatic LN burden is an important predictor of survival in patients with LHC. A proposed N classification using the number of positive LNs and ENE might improve the LHC survival prediction.

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References

  • Ahn SH, Hong HJ, Kwon SY, Kwon KH, Roh JL, Ryu J, Park JH, Baek SK, Lee GH, Lee SY, Lee JC, Chung MK, Joo YH, Ji YB, Hah JH, Kwon M, Park YM, Song CM, Shin SC, Ryu CH, Lee DY, Lee YC, Chang JW, Jeong HM, Cho JK, Cha W, Chun BJ, Choi IJ, Choi HG, Lee KD (2017) Guidelines for the surgical management of laryngeal cancer: Korean Society of Thyroid-Head and Neck Surgery. Clin Exp Otorhinolaryngol 10(1):1–43

    Article  PubMed  PubMed Central  Google Scholar 

  • Amin MB, Greene FL, Byrd DR, Brookland RK, Washington MK (eds) (2017) AJCC cancer staging manual, 8th edn. Springer, New York, pp 149–161

    Google Scholar 

  • Apisarnthanarax S, Elliott DD, El-Naggar AK, Asper JA, Blanco A, Ang KK, Garden AS, Morrison WH, Rosenthal D, Weber RS, Chao KS (2006) Determining optimal clinical target volume margins in head-and-neck cancer based on microscopic extracapsular extension of metastatic neck nodes. Int J Radiat Oncol Biol Phys 64(3):678–683

    Article  PubMed  Google Scholar 

  • Bonomi MR, Blakaj A, Blakaj D (2018) Organ preservation for advanced larynx cancer: a review of chemotherapy and radiation combination strategies. Oral Oncol 86:301–306

    Article  PubMed  Google Scholar 

  • Colevas AD, Yom SS, Pfister DG, Spencer S, Adelstein D, Adkins D, Brizel DM, Burtness B, Busse PM, Caudell JJ, Cmelak AJ, Eisele DW, Fenton M, Foote RL, Gilbert J, Gillison ML, Haddad RI, Hicks WL, Hitchcock YJ, Jimeno A, Leizman D, Maghami E, Mell LK, Mittal BB, Pinto HA, Ridge JA, Rocco J, Rodriguez CP, Shah JP, Weber RS, Witek M, Worden F, Zhen W, Burns JL, Darlow SD (2018) NCCN guidelines insights: head and neck cancers, version 1.2018. J Natl Compr Canc Netw 16(5):479–490

    Article  PubMed  Google Scholar 

  • Denaro N, Merlano MC (2018) Immunotherapy in head and neck squamous cell cancer. Clin Exp Otorhinolaryngol 11(4):217–223

    Article  PubMed  PubMed Central  Google Scholar 

  • Divi V, Chen MM, Nussenbaum B, Rhoads KF, Sirjani DB, Holsinger FC, Shah JL, Hara W (2016a) Lymph node count from neck dissection predicts mortality in head and neck cancer. J Clin Oncol 34(32):3892–3897

    Article  PubMed  Google Scholar 

  • Divi V, Harris J, Harari PM, Cooper JS, McHugh J, Bell D, Sturgis EM, Cmelak AJ, Suntharalingam M, Raben D, Kim H, Spencer SA, Laramore GE, Trotti A, Foote RL, Schultz C, Thorstad WL, Zhang QE, Le QT, Holsinger FC (2016b) Establishing quality indicators for neck dissection: correlating the number of lymph nodes with oncologic outcomes (NRG Oncology RTOG 9501 and RTOG 0234). Cancer 122(22):3464–3471

    Article  PubMed  PubMed Central  Google Scholar 

  • Ebrahimi A, Gil Z, Amit M, Yen TC, Liao CT, Chaturvedi P, Agarwal JP, Kowalski LP, Kohler HF, Kreppel M, Cernea CR, Brandao J, Bachar G, Bolzoni Villaret A, Fliss D, Fridman E, Robbins KT, Shah JP, Patel SG, Clark JR (2014) The prognosis of N2b and N2c lymph node disease in oral squamous cell carcinoma is determined by the number of metastatic lymph nodes rather than laterality: evidence to support a revision of the American Joint Committee on Cancer staging system. Cancer 120(13):1968–1974

    Article  PubMed  Google Scholar 

  • Edge SB, Compton CC (2010) The American Joint Committee on Cancer: the 7th edition of the AJCC cancer staging manual and the future of TNM. Ann Surg Oncol 17(6):1471–1474

    Article  PubMed  Google Scholar 

  • Forastiere AA, Weber RS, Trotti A (2015) Organ preservation for advanced larynx cancer: issues and outcomes. J Clin Oncol 33(29):3262–3268

    Article  PubMed  PubMed Central  Google Scholar 

  • Heagerty PJ, Lumley T, Pepe MS (2000) Time-dependent ROC curves for censored survival data and a diagnostic marker. Biometrics 56(2):337–344

    Article  CAS  PubMed  Google Scholar 

  • Ho AS, Kim S, Tighiouart M, Gudino C, Mita A, Scher KS, Laury A, Prasad R, Shiao SL, Van Eyk JE, Zumsteg ZS (2017) Metastatic lymph node burden and survival in oral cavity cancer. J Clin Oncol 35(31):3601–3609

    Article  PubMed  PubMed Central  Google Scholar 

  • Ho AS, Kim S, Tighiouart M, Gudino C, Mita A, Scher KS, Laury A, Prasad R, Shiao SL, Ali N, Patio C, Mallen-St Clair J, Van Eyk JE, Zumsteg ZS (2018) Association of quantitative metastatic lymph node burden with survival in hypopharyngeal and laryngeal cancer. JAMA Oncol 4(7):985–989

    Article  PubMed  Google Scholar 

  • Hothorn T, Hornik K, Zeileis A (2006) Unbiased recursive partitioning: a conditional inference framework. J Comput Graph Stat 15(3):651–674

    Article  Google Scholar 

  • Jakobsen J, Hansen O, Jorgensen KE, Bastholt L (1998) Lymph node metastases from laryngeal and pharyngeal carcinomas—calculation of burden of metastasis and its impact on prognosis. Acta Oncol 37(5):489–493

    Article  CAS  PubMed  Google Scholar 

  • Jones D, Pereira ER, Padera TP (2018) Growth and immune evasion of lymph node metastasis. Front Oncol 8:36

    Article  PubMed  PubMed Central  Google Scholar 

  • Joo YH, Cho KJ, Kim SY, Kim MS (2015) Prognostic significance of lymph node density in patients with hypopharyngeal squamous cell carcinoma. Ann Surg Oncol 22(Suppl 3):S1014–S1019

    Article  PubMed  Google Scholar 

  • Joo YH, Cho JK, Koo BS, Kwon M, Kwon SK, Kwon SY, Kim MS, Kim JK, Kim H, Nam I, Roh JL, Park YM, Park IS, Park JJ, Shin SC, Ahn SH, Won S, Ryu CH, Yoon TM, Lee G, Lee DY, Lee MC, Lee JK, Lee JC, Lim JY, Chang JW, Jang JY, Chung MK, Jung YS, Cho JG, Choi YS, Choi JS, Lee GH, Chung PS (2019) Guidelines for the surgical management of oral cancer: Korean Society of Thyroid-Head and Neck Surgery. Clin Exp Otorhinolaryngol 12(2):107–144

    Article  PubMed  PubMed Central  Google Scholar 

  • Jover-Espla AG, Palazon-Bru A, Folgado-de la Rosa DM, Severa-Ferrandiz G, Sancho-Mestre M, de Juan-Herrero J, Gil-Guillen VF (2018) A predictive model for recurrence in patients with glottic cancer implemented in a mobile application for Android. Oral Oncol 80:82–88

    Article  PubMed  Google Scholar 

  • Kim BH, Park SJ, Jeong WJ, Ahn SH (2018) Comparison of treatment outcomes for T3 glottic squamous cell carcinoma: a meta-analysis. Clin Exp Otorhinolaryngol 11(1):1–8

    Article  PubMed  PubMed Central  Google Scholar 

  • Kligerman J, Olivatto LO, Lima RA, Freitas EQ, Soares JR, Dias FL, Melo LE, Sa GM, Duccini E (1995) Elective neck dissection in the treatment of T3/T4 N0 squamous cell carcinoma of the larynx. Am J Surg 170(5):436–439

    Article  CAS  PubMed  Google Scholar 

  • Koch WM (2000) Head and neck surgery in the era of organ preservation therapy. Semin Oncol 27(4 Suppl 8):5–12

    CAS  PubMed  Google Scholar 

  • Kuo P, Mehra S, Sosa JA, Roman SA, Husain ZA, Burtness BA, Tate JP, Yarbrough WG, Judson BL (2016) Proposing prognostic thresholds for lymph node yield in clinically lymph node-negative and lymph node-positive cancers of the oral cavity. Cancer 122(23):3624–3631

    Article  PubMed  Google Scholar 

  • Qian W, Zhu G, Wang Y, Wang X, Ji Q, Wang Y, Dou S (2014) Multi-modality management for loco-regionally advanced laryngeal and hypopharyngeal cancer: balancing the benefit of efficacy and functional preservation. Med Oncol 31(9):178

    Article  CAS  PubMed  Google Scholar 

  • Roberts TJ, Colevas AD, Hara W, Holsinger FC, Oakley-Girvan I, Divi V (2016) Number of positive nodes is superior to the lymph node ratio and American Joint Committee on Cancer N staging for the prognosis of surgically treated head and neck squamous cell carcinomas. Cancer 122(9):1388–1397

    Article  PubMed  Google Scholar 

  • Suzuki H, Matoba T, Hanai N, Nishikawa D, Fukuda Y, Koide Y, Hasegawa Y (2016) Lymph node ratio predicts survival in hypopharyngeal cancer with positive lymph node metastasis. Eur Arch Otorhinolaryngol 273(12):4595–4600

    Article  PubMed  Google Scholar 

  • Tomik J, Skladzien J, Modrzejewski M (2001) Evaluation of cervical lymph node metastasis of 1400 patients with cancer of the larynx. Auris Nasus Larynx 28(3):233–240

    Article  CAS  PubMed  Google Scholar 

  • Vatcheva KP, Lee M, McCormick JB, Rahbar MH (2016) Multicollinearity in regression analyses conducted in epidemiologic studies. Epidemiology (Sunnyvale) 6(2):227

    Article  Google Scholar 

  • Zheng CM, Ji YB, Song CM, Ge MH, Tae K (2018) Number of metastatic lymph nodes and ratio of metastatic lymph nodes to total number of retrieved lymph nodes are risk factors for recurrence in patients with clinically node negative papillary thyroid carcinoma. Clin Exp Otorhinolaryngol 11(1):58–64

    Article  PubMed  Google Scholar 

  • Zumsteg ZS, Luu M, Kim S, Tighiouart M, Mita A, Scher KS, Lu DP, Shiao SL, Mallen-St Clair J, Ho AS (2019) Quantitative lymph node burden as a ‘very-high-risk’ factor identifying head and neck cancer patients benefiting from postoperative chemoradiation. Ann Oncol 30(1):76–84

    Article  CAS  PubMed  Google Scholar 

Download references

Funding

This study was supported by the National Research Foundation of Korea (NRF) grant, funded by the Ministry of Science and ICT (MSIT), the Government of Korea (no. 2019R1A2C2002259) (J.-L.R.).

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Authors and Affiliations

  1. Department of Otolaryngology, Asan Medical Center, University of Ulsan College of Medicine, 88 Olympic-ro 43-gil, Songpa-gu, Seoul, 05505, Republic of Korea

    Yeonjoo Choi, Manal Bin-Manie, Jong-Lyel Roh, Yoon Se Lee, Seung-Ho Choi, Soon Yuhl Nam & Sang Yoon Kim

  2. Department of Pathology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea

    Kyung-Ja Cho

  3. Department of Otolaryngology Head and Neck Surgery, King Saud University, Riyadh, Saudi Arabia

    Manal Bin-Manie

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  1. Yeonjoo Choi
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  2. Manal Bin-Manie
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  3. Jong-Lyel Roh
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Correspondence to Jong-Lyel Roh.

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The authors have no conflict of interest to disclose.

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All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional research board and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. This article does not contain any studies with animals performed by any of the authors. Informed consent from all individual participants was waived because of the retrospective nature of this study.

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432_2019_2990_MOESM1_ESM.tif

Kaplan–Meier curves estimating overall survival according to the proposed nodal staging system and primary tumour locations of the larynx (A) and hypopharynx (B). Log-rank test, P < 0.05. ENE, extra-nodal extension; LN, lymph node (TIFF 2433 kb)

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Choi, Y., Bin-Manie, M., Roh, JL. et al. Metastatic lymph node burden predictive of survival in patients undergoing primary surgery for laryngeal and hypopharyngeal cancer. J Cancer Res Clin Oncol 145, 2565–2572 (2019). https://doi.org/10.1007/s00432-019-02990-4

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  • DOI: https://doi.org/10.1007/s00432-019-02990-4

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