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01-11-2017 | Original Article

Impact of postoperative radiotherapy and HER2/new overexpression in salivary duct carcinoma

A monocentric clinicopathologic analysis

Authors: Dr. med. Marlen Haderlein, Claudia Scherl, Sabine Semrau, Sebastian Lettmaier, Markus Hecht, Ramona Erber, Heinrich Iro, Rainer Fietkau, Abbas Agaimy

Published in: Strahlentherapie und Onkologie | Issue 11/2017

Abstract

Aim

Retrospective Investigation of the prognostic relevance of clinicopathologic parameters in patients with salivary duct carcinoma (SDC).

Methods

An experienced pathologist reviewed 67 patients with de novo SDC or SDC ex pleomorphic adenoma. Paraffin-embedded tumor samples were examined by immunohistochemistry for expression of HER2/neu, androgen (AR), progesterone (PR), estrogen (ER), epidermal growth factor (EGFR) and programmed death ligand 1 (PD-L1-R) receptor. In 45 patients who had cM0 and follow-up data available, survival rates were calculated (Kaplan–Meier method) and prognostic variables were analyzed (univariate analysis: log-rank test; multivariate analysis: Cox-regression analysis).

Results

Overexpression of HER2/neu, AR, ER, PR, EGFR, PD-L1-R was found in 25.4%, 84%, 0%, 0%, 17.9%, 16.4% of patients. Overall (OS), disease-free (DFS), distant-metastases-free survival (DMFS) and locoregional control (LRC) were 92.3/72.4/56.9%, 78.2/58.1/58.1%, 85.4/65.2/65.2% and 89.7/81.9/81.9% after 1/3/5 years (medial follow-up 26 months). In univariate analysis a positive resection margin (p = 0.008) and no postoperative radiotherapy (p = 0.001) predict an increased locoregional recurrence rate. In multivariate analysis only postoperative radiotherapy is statistically significant (p = 0.004). Presence of lymph node metastases, a lymph node density >4 and HER2/neu overexpression predict decreased DFS and DMFS. In multivariate HER2/neu overexpression was the only significant predictor for reduced DFS (p = 0.04) and DMFS (p = 0.02).

Conclusion

Postoperative radiotherapy is the only significant predictor for LRC. HER2/neu receptor expression is an independent prognostic factor for decreased DFS and DMFS in patients with SDC. In addition to radio(chemo)therapy, intensified first-line treatment regimens should also be evaluated in the future.

Spitz MR, Batsakis JG (1984) Major salivary gland carcinoma. Descriptive epidemiology and survival of 498 patients. Arch Otolaryngol 110:45–49CrossRefPubMed

Gallo O, Franchi A, Bottai GV, Fini-Storchi I, Tesi G, Boddi V (1997) Risk factors for distant metastases from carcinoma of the parotid gland. Cancer 80:844–851CrossRefPubMed

Ali S, Bryant R, Palmer FL et al (2015) Distant metastases in patients with carcinoma of the major salivary glands. Ann Surg Oncol 22:4014–4019CrossRefPubMedPubMedCentral

Haderlein M, Scherl C, Semrau S et al (2016) High-grade histology as predictor of early distant metastases and decreased disease-free survival in salivary gland cancer irrespective of tumor subtype. Head Neck 38(Suppl 1):E2041–8CrossRefPubMed

Jayaprakash V, Merzianu M, Warren GW et al (2014) Survival rates and prognostic factors for infiltrating salivary duct carcinoma: Analysis of 228 cases from the Surveillance, Epidemiology, and End Results database. Head Neck 36:694–701CrossRefPubMed

Otsuka K, Imanishi Y, Tada Y et al (2016) Clinical outcomes and prognostic factors for salivary duct carcinoma: a multi-institutional analysis of 141 patients. Ann Surg Oncol 23:2038–2045CrossRefPubMedPubMedCentral

Luk PP, Weston JD, Yu B et al (2016) Salivary duct carcinoma: Clinicopathologic features, morphologic spectrum, and somatic mutations. Head Neck 38(Suppl 1):E1838–47CrossRefPubMed

Terhaard CH, Lubsen H, Rasch CR et al (2005) The role of radiotherapy in the treatment of malignant salivary gland tumors. Int J Radiat Oncol Biol Phys 61:103–111CrossRefPubMed

Garden AS, Weber RS, Morrison WH, Ang KK, Peters LJ (1995) The influence of positive margins and nerve invasion in adenoid cystic carcinoma of the head and neck treated with surgery and radiation. Int J Radiat Oncol Biol Phys 32:619–626CrossRefPubMed

10.

Mao MH, Zhang JG, Zhang J et al (2014) Postoperative [(1)(2)(5)I] seed brachytherapy in the treatment of acinic cell carcinoma of the parotid gland: with associated risk factors. Strahlenther Onkol 190:1008–1014CrossRefPubMed

11.

Mao MH, Zhang JG, Zheng L et al (2015) The incidence of radioepidermitis and the dose-response relationship in parotid gland cancer patients treated with 125I seed brachytherapy: incidence of radioepidermitis and the dose-response relationship. Strahlenther Onkol 191:26–33CrossRefPubMed

12.

Lagha A, Chraiet N, Ayadi M et al (2012) Systemic therapy in the management of metastatic or advanced salivary gland cancers. Head Neck Oncol 4:19CrossRefPubMedPubMedCentral

13.

Cros J, Sbidian E, Hans S et al (2013) Expression and mutational status of treatment-relevant targets and key oncogenes in 123 malignant salivary gland tumours. Ann Oncol 24:2624–2629CrossRefPubMed

14.

Wang K, Russell JS, McDermott JD et al (2016) Profiling of 149 salivary duct carcinomas, carcinoma ex pleomorphic adenomas, and adenocarcinomas, not otherwise specified reveals actionable genomic alterations. Clin Cancer Res 22(24):6061–6066CrossRefPubMed

15.

Masubuchi T, Tada Y, Maruya S et al (2015) Clinicopathological significance of androgen receptor, HER2, Ki-67 and EGFR expressions in salivary duct carcinoma. Int J Clin Oncol 20:35–44CrossRefPubMed

16.

Williams L, Thompson LD, Seethala RR et al (2015) Salivary duct carcinoma: the predominance of apocrine morphology, prevalence of histologic variants, and androgen receptor expression. Am J Surg Pathol 39:705–713CrossRefPubMed

17.

Mitani Y, Rao PH, Maity SN et al (2014) Alterations associated with androgen receptor gene activation in salivary duct carcinoma of both sexes: potential therapeutic ramifications. Clin Cancer Res 20:6570–6581CrossRefPubMedPubMedCentral

18.

Jaehne M, Roeser K, Jaekel T, Schepers JD, Albert N, Loning T (2005) Clinical and immunohistologic typing of salivary duct carcinoma: a report of 50 cases. Cancer 103:2526–2533CrossRefPubMed

19.

Clauditz TS, Reiff M, Gravert L et al (2011) Human epidermal growth factor receptor 2 (HER2) in salivary gland carcinomas. Pathology 43:459–464CrossRefPubMed

20.

Di Palma S, Simpson RH, Marchio C et al (2012) Salivary duct carcinomas can be classified into luminal androgen receptor-positive, HER2 and basal-like phenotypes. Histopathology 61:629–643CrossRefPubMed

21.

Simpson RH (2013) Salivary duct carcinoma: new developments--morphological variants including pure in situ high grade lesions; proposed molecular classification. Head Neck Pathol 7(Suppl 1):S48–58CrossRefPubMed

22.

Xu J, Sun HH, Fletcher CD et al (2016) Expression of programmed cell death 1 Ligands (PD-L1 and PD-L2) in Histiocytic and dendritic cell disorders. Am J Surg Pathol 40:443–453CrossRefPubMed

23.

Mukaigawa T, Hayashi R, Hashimoto K, Ugumori T, Hato N, Fujii S (2016) Programmed death ligand-1 expression is associated with poor disease free survival in salivary gland carcinomas. J Surg Oncol 114:36–43CrossRefPubMed

24.

Roh JL, Lee JI, Choi SH et al (2014) Prognostic factors and oncologic outcomes of 56 salivary duct carcinoma patients in a single institution: high rate of systemic failure warrants targeted therapy. Oral Oncol 50:e64–6CrossRefPubMed

25.

Johnston ML, Huang SH, Waldron JN et al (2016) Salivary duct carcinoma: treatment, outcomes, and patterns of failure. Head Neck 38(Suppl 1):E820–6CrossRefPubMed

26.

Gilbert MR, Sharma A, Schmitt NC et al (2016) A 20-year review of 75 cases of salivary duct carcinoma. JAMA Otolaryngol Head Neck Surg 142:489–495CrossRefPubMedPubMedCentral

27.

Han MW, Roh JL, Choi SH et al (2015) Prognostic factors and outcome analysis of salivary duct carcinoma. Auris Nasus Larynx 42:472–477CrossRefPubMed

28.

Kim JY, Lee S, Cho KJ et al (2012) Treatment results of post-operative radiotherapy in patients with salivary duct carcinoma of the major salivary glands. Br J Radiol 85:e947–52CrossRefPubMedPubMedCentral

29.

Shinoto M, Shioyama Y, Nakamura K et al (2013) Postoperative radiotherapy in patients with salivary duct carcinoma: clinical outcomes and prognostic factors. J Radiat Res 54:925–930CrossRefPubMedPubMedCentral

30.

Schiffmann J, Lesmana H, Tennstedt P et al (2015) Additional androgen deprivation makes the difference: Biochemical recurrence-free survival in prostate cancer patients after HDR brachytherapy and external beam radiotherapy. Strahlenther Onkol 191:330–337CrossRefPubMed

Title: Impact of postoperative radiotherapy and HER2/new overexpression in salivary duct carcinoma
A monocentric clinicopathologic analysis
Authors: Dr. med. Marlen Haderlein
Claudia Scherl
Sabine Semrau
Sebastian Lettmaier
Markus Hecht
Ramona Erber
Heinrich Iro
Rainer Fietkau
Abbas Agaimy
Publication date: 01-11-2017
Publisher: Springer Berlin Heidelberg
Published in: Strahlentherapie und Onkologie / Issue 11/2017
Print ISSN: 0179-7158
Electronic ISSN: 1439-099X
DOI: https://doi.org/10.1007/s00066-017-1196-8

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Impact of postoperative radiotherapy and HER2/new overexpression in salivary duct carcinoma

A monocentric clinicopathologic analysis

Abstract

Aim

Methods

Results

Conclusion

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Aim

Methods

Results

Conclusion

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