The online version of this article (https://doi.org/10.1186/s13014-018-1130-y) contains supplementary material, which is available to authorized users.
The patterns of nodal relapse in submandibular gland carcinoma (SMGC) patients treated with postoperative radiotherapy (PORT) remain unclear. This study aims to investigate the nodal failure patterns and the utility of elective nodal irradiation (ENI) in SMGC patients undergoing PORT.
We retrospectively enrolled 65 SMGC patients who underwent PORT between 2000 and 2014. The nodal failure sites in relation to irradiation fields and pathological parameters were analyzed. ENI regions were categorized into three bilateral echelons (first, levels I–II; second, level III; and third, levels IV–V). Extended ENI was defined as coverage of at least the immediately adjacent uninvolved echelons bilaterally; otherwise, limited ENI was administered.
Thirty patients (46%) were stage III–IV, and 18 (28%) were pN+. Neck irradiation included limited (72%) and extended ENI (28%). With a median follow-up of 79 months, 11 patients (17%) developed nodal failures (ipsilateral, N = 6; contralateral, N = 7), 7 (64%) of whom relapsed in the adjacent uninvolved echelons. We identified pN+ (P = 0.030), extranodal extension (ENE, P = 0.002), pT3–4 (P = 0.021), and lymphovascular invasion (LVI, P = 0.004) as significant predictors of contralateral neck recurrence. Extended ENI significantly improved regional control (RC) in patients with pN+ (P = 0.003), ENE (P = 0.022), pT3–4 (P = 0.044), and LVI (P = 0.014), and improved disease-free survival (DFS) in patients with pN+ (P = 0.034). For patients with ≥2 coincident adverse factors, extended ENI significantly increased RC (P < 0.001), distant metastasis-free survival (P = 0.019), and DFS (P = 0.007); conversely, no nodal recurrence was observed in patients without these adverse factors, even when only the involved echelon was irradiated.
Nodal failure is not uncommon in SMGC patients treated with PORT if pN+, ENE, pT3–4, and LVI are present. Extended ENI should be considered, particularly in patients with multiple pathological adverse factors.
Additional file 1: Figure S1. Perineural tumor recurrence at (A) lingual (solid arrow), inferior alveolar (arrow head) and facial (dashed arrow) nerves (#12) and (B) hypoglossal nerve (#11). (PDF 63 kb)13014_2018_1130_MOESM1_ESM.docx
Additional file 2: Table S1. Patient characteristics in selected patients with risk factors. (DOCX 334 kb)13014_2018_1130_MOESM2_ESM.pdf
Bhattacharyya N. Survival and prognosis for cancer of the submandibular gland. J Oral and Maxillofac Surg. 2004;62:427–30. CrossRef
Wahlberg P, Anderson H, Biörklund A, et al. Carcinoma of the parotid and submandibular glands—a study of survival in 2465 patients. Oral Oncol. 2002;38:706–13. CrossRef
Spiro RH. Salivary neoplasms: overview of a 35-year experience with 2,807 patients. Head Neck Surg. 1986;8:177–84. CrossRef
Adelstein DJ, Koyfman SA, El-Naggar AK, Hanna EY. Biology and Management of Salivary Gland Cancers. Semin Radiat Oncol. 2012;22:245–53. CrossRef
Mendenhall WM, Morris CG, Amdur RJ, et al. Radiotherapy alone or combined with surgery for salivary gland carcinoma. Cancer. 2005;103:2544–50. CrossRef
Terhaard CH, Lubsen H, Rasch CR, et al. The role of radiotherapy in the treatment of malignant salivary gland tumors. Int J Radiat Oncol Biol Phys. 2005;61:103–11. CrossRef
Zeidan YH, Pekelis L, An Y, et al. Survival benefit for adjuvant radiation therapy in minor salivary gland cancers. Oral Oncol. 2015;51:438–45. CrossRef
Terhaard CH, Lubsen H, Van der Tweel I, et al. Salivary gland carcinoma: independent prognostic factors for locoregional control, distant metastases, and overall survival: results of the Dutch head and neck oncology cooperative group. Head Neck. 2004;26:681–93. CrossRef
Armstrong JG, Harrison LB, Spiro RH, et al. Malignant tumors of major salivary gland origin. A matched-pair analysis of the role of combined surgery and postoperative radiotherapy. Arch Otolaryngol Head Neck Surg. 1990;116:290–3. CrossRef
Armstrong JG, Harrison LB, Thaler HT, et al. The indications for elective treatment of the neck in cancer of the major salivary glands. Cancer. 1992;69:615–9. CrossRef
Ferlito A, Pellitteri PK, Robbins KT, et al. Management of the neck in cancer of the major salivary glands, thyroid and parathyroid glands. Acta Otolaryngol. 2002;122:673–8. CrossRef
Chen AM, Garcia J, Lee NY, et al. Patterns of nodal relapse after surgery and postoperative radiation therapy for carcinomas of the major and minor salivary glands: what is the role of elective neck irradiation? Int J Radiat Oncol Biol Phys. 2007;67:988–94. CrossRef
Chen AM, Granchi PJ, Garcia J, et al. Local-regional recurrence after surgery without postoperative irradiation for carcinomas of the major salivary glands: implications for adjuvant therapy. Int J Radiat Oncol Biol Phys. 2007;67:982–7. CrossRef
Zbären P, Schüpbach J, Nuyens M, Stauffer E. Elective neck dissection versus observation in primary parotid carcinoma. Otolaryngol Head Neck Surg. 2005;132:387–91. CrossRef
Vander Poorten VL, Balm AJ, Hilgers FJ, et al. The development of a prognostic score for patients with parotid carcinoma. Cancer. 1999;85:2057–67. CrossRef
Régis De Brito Santos I, Kowalski LP, Cavalcante De Araujo V, et al. Multivariate analysis of risk factors for neck metastases in surgically treated parotid carcinomas. Arch Otolaryngol Head Neck Surg. 2001;127:56–60. CrossRef
Han MW, Cho K-J, Roh J-L, et al. Patterns of lymph node metastasis and their influence on outcomes in patients with submandibular gland carcinoma. J Surg Oncol. 2012;106:475–80. CrossRef
Group IHaNS. Cervical lymph node metastasis in adenoid cystic carcinoma of the major salivary glands. J Laryngol Otol. 2017;131:96–105. CrossRef
Lin T-C, Tsou Y-A, Bau D-T, Tsai M-H. Factors influencing contralateral neck metastasis in oral squamous cell carcinoma. Formos J Surg. 2012;45:83–7. CrossRef
Dias FL, Lima RA, Kligerman J, et al. Relevance of skip metastases for squamous cell carcinoma of the oral tongue and the floor of the mouth. Otolaryngol Head Neck Surg. 2006;134:460–5. CrossRef
Pimenta Amaral TM, da Silva Freire AR, Carvalho AL, et al. Predictive factors of occult metastasis and prognosis of clinical stages I and II squamous cell carcinoma of the tongue and floor of the mouth. Oral Oncol. 2004;40:780–6. CrossRef
Liao C-T, Chang J-C, Wang H-M, et al. Analysis of risk factors of predictive local tumor control in oral cavity cancer. Ann Surg Oncol. 2008;15:915–22. CrossRef
Hsieh C-E, Lin C-Y, Lee L-Y, et al. Postoperative radiotherapy with or without concurrent chemotherapy for salivary gland carcinomas. Therapeut Radiol Oncol. 2015;22:89–91.
Tsan D-L, Lin C-Y, Kang C-J, et al. The comparison between weekly and three-weekly cisplatin delivered concurrently with radiotherapy for patients with postoperative high-risk squamous cell carcinoma of the oral cavity. Radiat Oncol. 2012;7:215. CrossRef
Hsieh C-E, Lin C-Y, Lee L-Y, et al. Adding concurrent chemotherapy to postoperative radiotherapy improves locoregional control but not overall survival in patients with salivary gland adenoid cystic carcinoma—a propensity score matched study. Radiat Oncol. 2016;11:1–10. CrossRef
Johnston ML, Huang SH, Waldron JN, et al. Salivary duct carcinoma: treatment, outcomes, and patterns of failure. Head Neck. 2016;38:E820–6. CrossRef
Stennert E, Kisner D, Jungehuelsing M, et al. High incidence of lymph node metastasis in major salivary gland cancer. Arch Otolaryngol Head Neck Surg. 2003;129:720–3. CrossRef
Mallik S, Agarwal J, Gupta T, et al. Prognostic factors and outcome analysis of submandibular gland cancer: a clinical audit. J Oral Maxillofac Surg. 2010;68:2104–10. CrossRef
Storey MR, Garden AS, Morrison WH, et al. Postoperative radiotherapy for malignant tumors of the submandibular gland. Int J Radiat Oncol Biol Phys. 2001;51:952–8. CrossRef
Huang B-S, Chen W-Y, Hsieh C-E, et al. Outcomes and prognostic factors for surgery followed by modern radiation therapy in parotid gland carcinomas. Jpn J Clin Oncol. 2016;46:832–8. CrossRef
Bjorndal K, Krogdahl A, Therkildsen MH, et al. Salivary gland carcinoma in Denmark 1990-2005: a national study of incidence, site and histology. Results of the Danish head and neck Cancer group (DAHANCA). Oral Oncol. 2011;47:677–82. CrossRef
Barrett AW, Speight PM. Perineural invasion in adenoid cystic carcinoma of the salivary glands: a valid prognostic indicator? Oral Oncol. 2009;45:936–40. CrossRef
Chen AM, Bucci MK, Weinberg V, et al. Adenoid cystic carcinoma of the head and neck treated by surgery with or without postoperative radiation therapy: prognostic features of recurrence. Int J Radiat Oncol Biol Phys. 2006;66:152–9. CrossRef
- Nodal failure patterns and utility of elective nodal irradiation in submandibular gland carcinoma treated with postoperative radiotherapy - a multicenter experience
Joseph Tung-Chieh Chang
- BioMed Central
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